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RC857   RS7  The  pancreas:  Its  s 


Columbia  Zinitiersfitp 
College  of  ^fjpgiciang  anb  ^urgeonjJ 


i^eference  Hibvaxp 


2>^  wl  3.ir 


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'A-/;^.^^ 


THE  PANCREAS 

ITS  SURGERY  AND  PATHOLOGY 


A.  W.  MAYO  ROBSON,  D.Sc.  (Leeds),  F.R.C.S.  (Eng.) 

LONDON 


P.  J.  CAMMIDGE,  M.B.  (Lond.),  D.RH.  (Camb.) 

LONDON 


ILLUSTRATED 


PHILADELPHIA  AND   LONDON 

W.  B.  SAUNDERS  COMPANY 

1907 


Copyright,  1907,  by  W.  B.  Saunders  Company 


Registered  at  Stationers'  Hall,  London,  England 


PRINTED    IN     PHILADELPHIA 


PREFACE 


Our  present  knowledge  of  the  physiology,  pathology, 
and  surgery  of  the  pancreas,  like  so  many  other  advances 
in  medicine  in  recent  years,  was  rendered  possible  by  the 
beneficent  work  of  Lister.  So  long  as  clinical  observa- 
tion was  only  capable  of  being  checked  by  the  experience 
of  the  post-mortem  room,  and  by  an  occasional  accidental 
experiment  on  the  living  subject,  the  important  and  com- 
plex part  that  the  pancreas  plays  in  the  physiology  of 
the  body  remained  unsuspected,  and  descriptions  of  the 
diseases  to  which  it  is  liable  were  confined  to  a  few  lines 
on  malignant  disease,  cysts,  and  calculi.  Animal  ex- 
periments, now  rendered  safe  by  antiseptic  surgery  and 
improved  technique,  have  thrown  a  flood  of  light  on  the 
physiology  of  the  organ  and  elevated  it  from  the  position 
of  a  mere  accessory  digestive  gland  to  the  rank  of  a  struc- 
ture indispensable  for  the  metaboHc  needs  of  the  organ- 
ism. The  numerous  laparotomies  undertaken  in  recent 
years  have  afforded  the  surgeon  opportunities  of  observing 
and  handling  the  living  organ,  both  in  health  and  disease, 
and  a  comparison  of  the  conditions  noticed,  together  with 
a  closer  investigation  of  the  symptoms  and  after-histories 
of  the  cases,  has  very,  considerably  widened  our  concep- 
tion of  the  pathological  changes  that  may  occur  in  the 
gland  and  afforded  a  basis  for  their  clinical  differentiation. 
Histological  and  post-mortem  inquiries,  stimulated  by 
the  impetus  thus  given,  have  still  further  increased  our 
knowledge,  and  confirmed  the  conclusions  of  the  bedside 
and  the  operating  theatre.  There  are  as  yet  many  points 
on  which  observers  are  not  agreed,  and  there  are  questions 

9 


lo  Preface 

which  still  call  for  elucidation,  but  the  enormous  literature 
of  to-day  as  compared  with  that  prior  to  1886,  when  Pro- 
fessor Senn  of  Chicago  published  his  valuable  experimental 
work  on  the  pancreas,  shows  the  great  advances  that  have 
been,  and  are  being,  made  in  the  subject. 

The  symptomatology  and  pathology  of  the  pancreas 
are  so  intimately  bound  up  with  the  physiology  and 
anatomy  of  the  gland,  and  these  again  are  rendered  so 
much  more  easily  understood  if  the  comparative  anatomy 
and  development  of  the  organ  are  borne  in  mind,  that 
we  have  prefaced  the  pathological  and  clinical  sections 
of  this  work  with  a  brief,  but  we  hope  sufficiently  compre- 
hensive and  accurate,  account  of  those  subjects. 

In  the  chapter  on  histology,  and  again  later  under  the 
heading  of  diabetes,  we  have  discussed  the  structure  and 
supposed  functions  of  those  characteristic  groups  of  cells 
known  as  the  islands  of  Langerhans.  In  doing  so  we  have 
endeavoured  to  impartially  summarise  the  evidence  for 
and  against  the  contending  views  that  are  held  with 
regard  to  them,  but,  as  will  be  gathered  from  the  text, 
we  personally  are  of  opinion  that  the  balance  of  available 
evidence  strongly  points  to  their  being  independent  struc- 
tures related  to  the  control  of  carbohydrate  metabolism 
within  the  body  that  the  pancreas  undoubtedly  exerts. 

A  thorough  comprehension  of  the  chemical  changes 
induced  in  the  body  by  diseases  of  the  pancreas  would 
include  a  knowledge  of  the  pathology  of  diabetes,  but  at 
present  we  are  still  in  the  dark  as  to  the  true  essentials 
of  that  condition.  Our  description  of  the  chemical 
pathology  of  the  pancreas  is  therefore  largely  confined  to 
the  condition  of  the  urine  and  fseces  found  to  accompany 
disease  of  the  gland,  and  although  we  have  now  devoted 
special  attention  to  this  subject  for  six  or  seven  years, 
we  are  conscious  that  as  yet  only  the  fringe  has  been 
touched  upon.  The  so-called  "pancreatic"  reaction  in 
the  urine  is  still  under   investigation.      The  improved 


Preface  1 1 

method  described  in  these  pages  is  undoubtedly  a  distinct 
advance  on  the  original  process  described  in  the  Arris 
and  Gale  lecture  of  1904,  but  it  is  not  yet  as  perfect 
as  it  might  be.  The  difficulty  of  the  investigation  is 
considerable,  for  the  quantity  of  material  to  be  obtained 
from  any  one  case,  even  when  a  well-marked  reaction  is 
given,  has  proved  to  be  small,  and  it  is  only  by  collecting 
very  large  amounts  of  urine  from  suitable  cases,  whenever 
they  have  occurred,  that  we  have  been  able  to  make  slow 
advances.  We  do  not  consider  that  at  present  we  are 
in  a  position  to  make  more  positive  statements  than  those 
expressed  in  the  chapter  on  chemical  pathology,  but  we 
hope  that  w^e  may  shortly  be  able  to  do  so.  In  our  own 
practice  we  never  rely  upon  the  "pancreatic"  reaction 
alone  in  making  a  diagnosis  of  pancreatitis  or  malignant 
disease  of  the  pancreas,  but  always  take  into  account  the 
results  of  a  complete  analysis  of  the  urine  and  a  chemical 
examination  of  the  faeces,  as  well  as  the  clinical  symptoms ; 
it  is  from  neglect  of  these  precautions,  and  under  the  false 
notion  that  the  "pancreatic"  reaction  was  claimed  to  be 
pathognomonic,  that  the  mistakes  made  by  some  writers 
.have  arisen.  The  examination  of  the  faeces  often  gives  im- 
portant confirmation  of  the  presence  or  absence  of  disease 
of  the  pancreas,  but  this  is  not  always  the  case,  and  the 
possible  causes  of  unexpected  results  described  in  the  text 
have  always  to  be  borne  in  mind.  The  question  of  the 
cause  of  the  absence  of  colour  in  the  stools  in  various  patho- 
logical conditions  has  excited  attention  for  many  years, 
and,  although  we  do  not  suggest  that  the  explanations 
our  investigations  and  observations  have  enabled  us  to 
make  are  true  of  all  cases  in  which  the  faeces  are  white, 
they  appear  to  be  so  for  pancreatic  disease. 

There  seems  to  be  an  impression  in  the  minds  of  nearly 
all  members  of  the  profession  that  diseases  of  the  pan- 
creas, excepting  some  of  the  grosser  lesions,  are  unrecog- 
nisable during  life,  but  we  venture  to  think  that  a  careful 


12 


Preface 


perusal  of  the  chapter  dealing  with  general  symptoma- 
tology and  diagnosis  will  show  that  while  no  single  sign 
or  symptom  is  characteristic  of  disease  of  the  pancreas, 
no  more  than  of  any  other  organ,  the  cumulative  evidence 
to  be  obtained  by  a  careful  investigation  of  the  history, 
clinical  symptoms,  and  signs,  and  the  indications  to  be 
obtained  by  the  methods  of  the  laboratory,  should  leave 
no  doubt  as  to  the  presence  or  absence  of  pancreatic 
trouble  in  any  particular  case  and,  in  the  large  majority, 
allow  of  a  definite  opinion  as  to  the  nature  of  the  lesion 
being  arrived  at. 

The  classification  of  inflammatory  lesions  of  the  pan- 
creas is  the  same  as  that  outlined  in  the  Hunterian 
Lectures  of  1904.  Increased  experience  has  only  served 
to  demonstrate  its  clinical  utility,  and  its  adoption  by 
subsequent  writers  shows  that  they  recognise  the  numer- 
ous forms  that  inflammation  of  the  pancreas  may  assume 
under  various  conditions.  We  have  emphasised  the  in- 
timate etiological  relation  existing  between  gall-stones 
and  pancreatitis  and  pointed  out  the  conditions  under 
which  biliary  calculi  in  the  common  bile-duct  are  likely 
to  cause,  and  will  fail  to  give  rise  to,  pancreatic  inflamma- 
tion. We  have  also  laid  stress  upon  the  no  less  important, 
but  less  commonly  recognised,  association  of  inflammation 
of  the  pancreas  with  catarrhal  conditions  of  the  upper  part 
of  the  gastro-intestinal  tract.  Pancreatitis  resulting  from 
a  duodenal  catarrh  may,  under  certain  conditions,  give 
rise  to  more  or  less  persistent  jaundice,  and,  in  our  ex- 
perience, is  the  most  common  cause  of  the  conditions 
usually  known  as  acute  and  chronic  "catarrhal"  jaundice. 

In  dealing  with  the  subject  of  diabetes  we  have  devoted 
much  space  to  a  consideration  of  its  relations  to  the  pan- 
creas, and  have  quoted  the  more  important  experimental 
evidence  and  clinical  work  bearing  upon  the  subject. 
Between  the  ofttimes  conflicting,  and  even  contradictory, 
statements  of  different  authors  it  is  difficult  to  arrive  at 


Preface  13 

any  very  definite  conclusions  as  to  the  frequency  of  pan- 
creatic lesions  in  diabetes  and  as  to  how  these  are  related 
to  the  disease,  but  one  fact  that  has  been  clearly  estab- 
lished is  that  a  small  portion  of  normal  gland  is  capable 
of  averting  the  onset  of  the  condition.  It  is  therefore 
important  that  diseases  of  the  pancreas  should  be  recog- 
nised at  the  earliest  possible  moment,  and  that  conditions 
likely  to  give  rise  to  pancreatic  lesions  should  be  radically 
treated  before  they  have  had  time  to  bring  about  perma- 
nent, and  may  be  progressive,  injury  of  the  gland.  For 
this  reason  we  strongly  advocate  the  early  treatment  of 
gall-stones,  especially  when  they  are  present  in  the  com- 
mon duct  and  an  examination  of  the  urine  and  faeces 
shows  that  a  pancreatic  lesion  exists.  The  very  striking 
increase  in  the  death-rate  from  diabetes  shown  by  the 
Registrar-General's  returns  is  possibly  not  unconnected 
with  the  greater  prevalence  of  digestive  disturbances  in 
recent  years,  and  we  therefore  think  that  duodenal  catarrh 
and  the  frequently  associated  catarrhal  pancreatitis 
always  call  for  prompt  attention. 

One  of  the  most  important  practical  results  that  has 
followed  from  modern  observations  on  the  pancreas  is 
the  recognition  of  the  very  close  similarity  of  the  symp- 
toms of  cancer  and  chronic  pancreatitis  in  the  head  of  the 
gland.  Many  cases  of  the  latter  have  in  the  past  been 
allowed  to  die  unoperated  on,  under  the  mistaken  impres- 
sion that  they  were  suffering  from  cancer,  and  our  ex- 
perience would  suggest  that,  even  at  the  present  time, 
there  are  many  who  do  not  realize  the  importance  of  a 
differential  diagnosis  between  the  two  conditions.  We 
have  dealt  with  this  subject  under  the  headings  of  chronic 
pancreatitis  and  cancer,  and  it  is  also  referred  to  in  the 
chapters  on  pathology  and  symptomatology. 

While  a  considerable  number  of  the  illustrations  in 
this  work  are  original  and  have  been  taken  from  prepara- 
tions in  our  own  possession,  we  are  deeply  indebted  to 


14  Preface 

the  various  museums  mentioned  for  permission  to  have 
drawings  or  photographs  made  from  their  specimens. 
Our  thanks  are  also  due  to  the  authors  and  publishers, 
to  whom  acknowledgments  are  made,  for  the  pictures 
appearing  above  their  names. 

To  the  end  of  each  chapter  we  have  appended  a  list 
of  the  more  important  papers  and  publications  bearing 
on  the  subjects  therein  discussed.  These  do  not  make 
any  pretense  at  completely  exhausting  the  bibliography, 
but  as  a  rule  merely  represent  an  alphabetical  list  of  the 
authors  mentioned  in  the  text.  In  writing  this  work  we 
have  laid  under  contribution  all  the  monographs  available 
to  us,  as  well  as  those  papers  that  have  appeared  on  the 
subject  in  the  current  literature.  We  have  endeavoured 
as  far  as  possible  to  credit  each  author  with  the  views  and 
cases  of  Avhich  he  has  written,  and  are  particularly  in- 
debted to  Opie,  Oser,  Rolleston,  and  Flexner.  A  certain 
number  of  illustrative  cases  and  illustrations  have  also 
been  taken  from  a  work  on  "  Diseases  of  the  Pancreas  "  by 
A.  W.  Mayo  Robson  and  B.  G.  A.  Moynihan  (Saunders 
&  Co.),  which  has  been  for  some  time  out  of  print.  Each 
case  and  opinion  has,  as  far  as  possible,  been  attributed 
to  its  original  author,  but  should  we  inadvertently  have 
misrepresented  any  of  the  writers  quoted,  or  attributed 
a  view  or  opinion  to  some  other  than  its  original  author, 
we  crave  forgiveness  and  ask  for  correction. 

A,  W.  Mayo  Robson. 
P.  J.  Cammidge. 

London,  Augtist,  igoy. 


CONTENTS 


CHAPTER   I  Page 

Comparative  Anatomy 17 

CHAPTER  II 
Anatomy 28 

CHAPTER  III 
Embryology 41 

CHAPTER  IV 
Anatomical  Anomalies 46 

CHAPTER  V 
Surgical  Anatomy 64 

CHAPTER  VI 
Histology 71 

CHAPTER  VII 
Physiology 96 

CHAPTER  VIII 
Pathology 126 

CHAPTER  IX 
Fat  Necrosis 190 

CHAPTER  X 
Chemical  Pathology 206 

CHAPTER  XI 
Diabetes 269 

CHAPTER  XII 
General  Symptomatology  and  Diagnosis 311 

CHAPTER  XIII 
Injuries 345 

CHAPTER  XIV 
Inflammatory  Affections  of  the  Pancreas 361 

15 


1 6  Contents 


CHAPTER  XV 


Page 


Acute  Pancreatitis  and  Subacute  Pancreatitis 384 

CHAPTER  XVI 
Chronic  Pancreatitis 412 

CHAPTER  XVII 
Pancreolithic  Catarrh  and  Pancreatic  Calculi 473 

CHAPTER  XVIII 
Pancreatic  Cysts 487 

CHAPTER  XIX 
Neoplasms 512 

Index  of  Authors 529 

l^OEX 537 


THE  PANCREAS 

ITS  SURGERY  AND  PATHOLOGY 


CHAPTER  I 
COMPARATIVE  ANATOMY 

In  unicellular  organisms  all  the  activities  of  life  are 
embraced  within  the  compass  of  a  simple  unit  of  living 
matter;  it  moves  by  contracting  its  substance,  it  draws 
back  from  hurtful  influences,  it  absorbs  oxygen,  it  en- 
gulfs and  digests  food,  and  gets  rid  of  the  waste  products 
of  its  metabolism.  But,  early  in  the  communal  life  of 
the  multicellular  metazoa,  a  tendency  is  seen  to  limit  the 
physiological  activities  of  the  groups  of  cells,  and  to  con- 
centrate special  functions  in  particular  areas.  As  we 
advance  up  the  scale  of  life  this  tendency  becomes  more 
and  more  marked,  and  these  aggregations  of  cells,  set 
apart  to  subserve  particular  purposes  in  the  economy  of 
the  body,  are  differentiated  as  distinct  organs.  The  more 
complicated  and  active  the  life  of  the  animal,  the  more 
numerous  are  its  organs,  for,  by  the  concentration  of 
the  activities  of  the  cells  on  the  performance  of  some 
special  work,  energy  is  economised,  in  the  same  way  as 
division  of  labour  in  the  commercial  world  is  found  to 
contribute  to  economy  of  production. 

One  of  the  most  primitive  areas  to  be  set  apart  for  the 

performance  of  a  special  function  is  that  which  deals 

with  the  absorption  of  food.     First  distinctly  seen  as  a 

mere  folding  in  of  the  surface  to  form  a  pouch,  it  assumes, 

2  17 


1 8         The  Pancreas:  Its  Surgery  and  Pathology 

in  most  of  the  metazoa,  the  form  of  a  canal  passing  through 
the  tissues  and  connected  with  the  external  world  by  an 
apeture  at  either  extremity.  The  cells  lining  the  alimen- 
tary area,  in  its  simplest  form,  show  but  little  differentia- 
tion of  structure,  and,  although  they  are  predominantly 
digestive  in  character,  they  have  not  lost  the  primitive 
and  many-sided  qualities  of  the  protozoon,  as  is  shown  by 
the  ease  with  which  a  change  of  environment  will  bring 
about  a  change  of  function,  so  that  those  which  were  pre- 
viously subsidiary  become  predominant.  In  the  higher 
forms  the  characters  of  the  cells  become  more  fixed,  their 
structure  is  modified  to  suit  their  special  work  and  sur- 
roundings, and  their  power  of  reverting  to  the  primitively 
complex  physiological,  but  anatomically  simple,  type  is 
lost. 

Up  to  the  echinoderms  there  is  no  indication  of  a  par- 
ticular concentration  of  the  digestive  powers  in  any  one 
part  of  the  alimentary  tract.  The  walls  may  be  pouched 
or  ridged,  to  increase  the  surface,  and  one  portion  may  be 
more  muscular  or  harder  than  another,  in  order  that  the 
food  may  be  better  ground  or  mixed,  but  the  whole  ex- 
tent of  the  tract  is  in  contact  with  its  contents,  and  no 
part  is  to  be  distinguished  as  especially  set  apart  for  the 
elaboration  of  digestive  ferments.  In  a  type  such  as  the 
starfish,  however,  such  glandular  structures  can  be  recog- 
nised. In  this  animal  five  branches  are  given  off  from 
the  pyloric  portion  of  the  stomach,  and  each  of  these  di- 
vides into  two  large  digestive  cseca.  The  glands  them- 
selves do  not  come  into  contact  with  the  food,  but  secrete 
a  ferment,  which  is  said  to  have  tryptic,  peptic,  and 
diastatic  powers,  thus  showing  the  first  definite  step  in 
the  further  differentiation  of  the  functions  of  digestion 
and  absorption. 

Most  of  the  Crustacea,  Insecta,  and  Mollusca  possess 
one  or 'more  pairs  of  similar  digestive  caeca,  or  glands, 
which  join  the  alimentary  tract  in  the  region  of  the  mid- 


Comparative  Anatomy 


19 


gut,  or  stomach.  Their  function  is  still  complex,  and  no 
advance  to  a  higher  and  simpler  physiological  type  than 
that  seen  in  the  starfish  is  to  be  recognised. 

In  the  lower  members  of  the  vertebrate  series  a  similar 
state  of  things  is  found,  and  even  in  certain  fishes  the 
length  of  the  intestine,  a  thickening  of  the  mucous  mem- 
brane of  the  duodenum,  or  the  inactive  nature  of  the 
species  renders  any  special  di- 
gestive glands  unnecessary.  In 
most  osseous  fishes,  however, 
there  is  a  well-defined  gland 
having  the  characters  and  func- 
tions of  a  liver,  and  in  addition 
an  extension  of  the  secreting 
surface  of  the  intestine  by  the 
presence  of  a  number  of  long, 
slender  pouches,  which  are  con- 
nected with  the  commencement 
of  the  duodenum.  These  differ 
in  length  and  width,  and,  while 
the  widest  are  sometimes  found 
to  be  filled  with  the  same  con- 
tents as  the  intestine,  the  nar- 
rowest serve  only  as  secreting 
organs,  and  are  apparently 
specialised  for  the  elaboration 
of  digestive  ferments.  Their 
number  and  arrangement  vary 
in  different  types.  In  the  sand- 
lance  there  is  only  one,  but  in  the  whiting  and  salmon 
there  are  a  hundred  or  more.  In  the  herring,  haddock, 
and  salmon  they  are  disposed  in  a  line  along  the  whole 
length  of  the  duodenum,  while  in  the  whiting  they  are 
arranged  in  a  circle  around  the  distal  end  of  the  pylorus. 
A  tendency  to  concentrate  these  intestinal  outgrowths 
into  a  more  typical  glandular  structure  is  seen  in  some 


Fig.  I.  —  Pyloric  ap- 
pendages of  the  salmon 
(after  Giinther). 


20         The  Pancreas:  Its  Surgery  and  Pathology 


members  of  the  class,  especially  in  the  more  active  types, 
in  which  rapid  and  complete  digestion  is  a  necessity. 
The  50  caeca  of  the  pilchard  open  into  the  duodenum  by 
30  orifices,  but  the  120  of  the  whiting  progressively  unite 
into  four  or  five  groups,  each  communicating  with  the 
duodenum  by  a  single  duct.     The  swordfish  has  but  two 

openings,  and  in  the  sturgeon  a 
single  wide  duct  terminates  by 
a  papilla  on  the  internal  sur- 
face of  the  duodenal  wall,  close 
to  the  ductus  choledochus.  The 
long,  slender,  ramified  caeca  are, 
in  the  two  last,  bound  loosely 
together  by  connective  tissue 
and  possess  a  rich  vascular  sup- 
ply, the  whole  being  enclosed 
in  a  capsule,  thus  corresponding 
in  structure  to  a  conglomerate 
gland  of  the  type  of  the  pan- 
creas. In  many  fishes  that 
have  typical  pyloric  caeca,  and 
in  some  that  do  not  possess 
these  structures,  there  exists  a 
conglomerate  glandular  organ 
opening  by  a  duct  into  the 
duodenum,  which  is  apparently 
the  true  homologue  of  the  pan- 
creas in  air-breathing  animals. 
A  large -lobed  structure  of  this 
description,  the  duct  of  which  is  so  intimately  connected 
with  the  bile-duct  that  both  appear  as  a  single  structure 
externally,  is  found  in  the  salmon.  In  the  catfish  it  is 
very  large,  and  the  bile-duct  passes  through  its  substance. 
In  the  plaice,  flounder,  gar-pike,  etc.,  it  is  situated  in  the 
mesentery  and  is  smaller,  but  its  duct  in  each  instance 
accompanies  the  terminal  portion  of  the  ductus  chole- 


Fig.  2. — Alimentary  canal 
of  the  whiting,  showing  the 
arrangement  of  the  pyloric 
caeca  (after  Owen). 


Comparative  Anatomy 


21 


dochus.  The  characters  of  this  organ  in  the  sturgeon 
have  already  been  referred  to.  A  similar  glandular  mass 
of  considerable  size,  lying  behind  the  stomach,  and  close 
to  the  spleen,  is  met  with  in  sharks  and  other  elasmo- 
branchs. 

The  liver  in  reptiles  is  proportionally  large,  and  they 


To. 


Fig.  3. — Pancreas  and  spleen  of  the  turtle  (after  Owen). 


possess  a  distinct  and  well-defined  pancreas.  The  lat- 
ter is  a  yellow  or  pink  gland,  consisting  of  many  acini, 
each  opening  into  a  small  duct.  These  ducts  unite  into 
larger  ducts,  and  these  again  form  a  common  channel, 
which  opens  into  the  intestine  with,  or  close  to,  the  bile- 
duct.     The  acini  round  the  smaller  ducts  are  aggregated 


22         The  Pancreas:  Its  Surgery  and  Pathology 


together  to  form  lobules,  and  the  lobules  are  again  col- 
lected into  lobes.  In  some  members  of  the  group  the 
pancreas  is  spread  out  in  the  duodenal  mesentery,  but  in 
most  serpents  and  lizards  it  has  a  compact  form;  in  the 
crocodile  it  is  divided  into  two  elongated  lobes,  and 
sometimes  communicates  with  the  duodenum  by  two 
distinct  ducts ;  in  the  turtle  the  pan- 
creatic duct  terminates  by  a  papilla 
opening  into  the  expanded  end  or 
ampulla  of  the  bile-duct.  The  pan- 
creas of  the  carnivorous  types  of  the 
reptilia  is  more  bulky  and  compact, 
forming  a  larger  proportion  of  the 
total  weight  of  the  animal  than  in 
the  vegetable-feeders. 

The  pancreas  of  birds  is  usually 
firmer  than  that  of  reptiles.  It  is 
also  relatively  larger,  probably  to 
compensate  for  the  absence  of  masti- 
cation and  the  salivary  digestion  of 
the  food.  It  is  long  and  narrow, 
lying  in  the  space  between  the  duo- 
denal loops,  and  generally  consists  of 
two,  and  sometimes  of  three,  por- 
tions. It  communicates  with  the  in- 
testine by  two,  and  occasionally  by 
three,  separate  ducts,  which  open 
near  the  hepatic  and  cystic  ducts. 

In  the  mammalia  the  pancreas  is 
more  plainly  of  the  conglomerate 
type.  It  is  paler,  and  of  a  firmer  structure,  than  in 
birds,  and  also  differs  by  the  development  of  a  part, 
stretching  towards  the  spleen,  which  is  more  or  less  dis- 
tinct from  that  lodged  within  the  duodenal  loop.  In 
the  simpler  members  of  the  series,  such  as  the  mar- 
supials, the  gland  is  bent  upon  itself,  running  from  the 


Fig.  4. — Pancreas 
and  duodenum  of 
goose  (after  Owen). 


Comparative  Anatomy 


23 


duodenum  to  the  spleen,  behind  the  stomach,  and  giving 
off  into  the  duodenal  mesentery  and  omental  folds  more 
or  less  numerous  processes.  The  main  duct  opens  into 
the  bile-duct,  the  bile  and  pancreatic  secretion  reaching 
the  intestine  through  a  common  opening. 

The  main  mass  of  the  gland  in  rodents  follows  the  curve 
of  the  duodenum,  but  sends  numerous  ramifying  processes 
into  the  mesentery.     The  main  duct,  into  which  the  minor 


fn 


Fig.  5. — Pancreas  of  the  rat  (after  Owen). 


channels  collect,  enters  the  duodenum  a  considerable 
distance  from  the  point  of  entry  of  the  bile-duct.  In  the 
beaver  18  inches  separates  the  papilla  of  the  biliary  pas- 
sage from  that  of  the  pancreatic  duct,  and  the  latter  is 
some  21  inches  from  the  pylorus.  A  small,  and  usually 
impermeable,  duct,  corresponding  to  the  main  channel 
of  the  pancreas  of  most  of  the  mammalia,  can,  in  some 
instances,  be  made  out  joining  the  intestine  in  the  neigh- 
bourhood of  the  biliary  papilla.     The  functioning  duct 


24         The  Pancreas:  Its  Surgery  and  Pathology 

in  this  group  probably  represents  one  of  the  lower  mem- 
bers of  the  series  of  digestive  cseca  found  arranged  along 
the  length  of  the  duodenum  in  some  fishes. 

The  pancreas  of  the  aquatic  mammals  (Cetacea)  is  long, 
narrow,  and  compact.  It  crosses  the  spine  at  the  root  of 
the  mesentery,  the  left  end  terminating  near  the  spleen, 

and  the  right  being  expanded 
and  adherent  to  the  curve  of 
the  duodenum.  The  pancre- 
atic duct  joins  the  bile-duct. 

The  transverse  or  splenic 
portion  of  the  gland  is  still 
better  developed  in  the  un- 
gulates, and,  in  this  order, 
forms  the  larger  part  of  the 
gland.  Its  duct,  which  is 
separate  from  that  of  the 
duodenal  part,  joins  with  the 
hepatic  duct  to  form  an  am- 
pulla before  entering  the  in- 
testine. The  smaller,  duode- 
nal portion  of  the  gland  lies 
at  right  angles  to  the  trans- 
verse part.  It  expands  down- 
^"^  wards  and  backwards  in  the 

pouchlf  the^lrham^'formed     ^^odenal  mesentery.    Its  duct 

by  the  union  of  the  common     enters   the   duodenum   about 

bile-duct  and  pancreatic  duct       ,.  j  •   j_  r  j-i 

(after  Owen).  "the    Same    distance   from  the 

pylorus  as  the  common  bile 
and  pancreatic  opening,  but  by  quite  a  distinct  aperture. 

The  divisions  of  the  pancreas  in  the  ruminants  are 
somewhat  less  well  defined,  the  gland  being  broader  and 
flatter  in  character. 

The  long,  narrow  pancreas  of  the  carnivora  shows  a 
well-marked  division  into  splenic  and  duodenal  sections, 
which  are  of  unequal  length.     The  splenic  part  is  straight 


Comparative  Anatomy 


25 


and  runs  transversely  across  the  spine ;  the  duodenal  seg- 
ment follows  the  curve  of  the  duodenum.  Both  are  cov- 
ered by  the  peritoneum.  In  most  members  of  the  order 
the  ducts  of  the  transverse  and  descending  portions  anas- 


Fig.  7. — Pancreas  of  the  dog,  dissected  to  show  the  relations  of  the 
common  bile-duct  and  pancreatic  ducts  and  their  openings  into  the 
duodenum. 


tomose  at  two  points,  and  the  main  duct  communicates 
with  the  bile-duct  before  entering  the  duodenum. 

The  pancreas  of  the  cat  and  dog  calls  for  special  men- 
tion, owing  to  the  frequent  use  made  of  these  animals  in 
experimental  work.     The  duodenal  part  of  the  gland  in 


Fig.  8.- — Dissection  of  an  abnormal  pancreas  of  a  dog,  showing  separate 
openings  for  the  common  bile-duct  and  two  pancreatic  ducts. 


the  dog  is  larger  than  the  splenic  portion,  which  it  joins 
at  right  angles.  As  a  rule,  the  smaller  duct  joins  with  the 
common  bile-duct  within  the  walls  of  the  duodenum,  but 
is  externally  quite  distinct.     The  larger  then  enters  the 


26        The  Pancreas:  Its  Surgery  and  Pathology 

bowel  half  an  inch  or  more  below.  Occasionally  the  bile- 
duct  and  two  pancreatic  ducts  have  separate  openings, 
as  in  the  case  of  a  dog  dissected  by  one  of  us.  In  the  cat 
there  is  a  large  duct,  communicating  with  both  sections 
of  the  gland,  which  joins  with  the  bile-duct,  and  enters 
the  duodenum  by  a  common  orifice  with  it.  A  smaller 
duct  is  also  present,  which  anastomoses  with  the  main 
channel  within  the  gland,  but  possesses  a  separate  open- 
ing into  the  intestine  a  short  distance  below.     Occasion- 


Fig.  9. — Pancreas  of  the  cat,  laid  open  to  show  the  main  ducts  and 
their  relation  to  a  large  vein  near  the  junction  of  the  two  ducts  (after 
DeWitt). 


ally  a  lateral  reservoir,  communicating  with  the  main 
channel  by  a  short  duct  just  before  its  junction  with  the 
bile-passage,  is  found. 

The  pancreas  of  the  anthropoidea  is  less  mobile  than 
in  any  other  group  of  animals,  and  is  found  to  be  more 
completely  applied  and  fixed  to  the  posterior  abdominal 
wall,  the  more  adapted  the  animal  is  to  the  upright  posi- 
tion. The  duodenal  part  is  reduced  to  an  enlargement 
termed  the  "head,"  while  the  splenic  portion  narrows  at 


Comparative  Anatomy  27 

its  termination  near  the  spleen  to  form  "the  tail."  The 
intervening  portion  forms  "the  body"  of  the  gland,  along 
the  thick  upper  border  of  which  run  the  splenic  artery 
and  vein.  The  main  duct  traverses  the  substance  of  the 
gland,  nearer  its  lower  than  its  upper  border,  and  usually 
communicates,  near  its  termination,  with  the  lesser  duct 
which  drains  the  head.  The  latter  may  have  a  separate 
entrance  into  the  duodenum,  placed  somewhat  nearer  the 
pylorus  than  the  papilla  by  which  the  main  pancreatic 
channel  and  bile-duct  open,  or  it  may  be  obliterated,  the 
whole  of  the  pancreatic  secretion,  including  that  from  the 
head,  then  finding  its  way  into  the  intestine  by  way  of  the 
common  opening. 

Rachford  has  pointed  out  that  the  nearer  an  animal 
approaches  to  the  purely  carnivorous  type,  the  more 
likely  are  the  bile  and  pancreatic  juice  to  be  passed  into 
the  intestine  through  a  common  opening,  and  the  closer 
is  this  opening  to  the  pylorus. 

Literature 

Giinther :   ' '  The  Study  of  Fishes. ' ' 

Owen:    "Comparative  Anatomy  and  Physiology  of  Vertebrates." 

Rachford:   Jour,  of  Physiol.,  xxv,  165. 

Schieffer:  "Du  Pancreas  dans  la  serie  animale,"  Th.  Montpellier,  1894. 

Thompson:   "Outlines  of  Zoology." 


CHAPTER  II 
ANATOMY 

The  greater  part  of  the  pancreas  in  man  lies  in  the 
epigastrium,  but  a  portion  of  the  body  and  the  tail  extend 
into  the  left  hypochondrium,  and  the  head  may  project 
into  the  umbilical  region. 

To  expose  the  organ  from  the  front  the  stomach  must 
be  detached  from  the  great  omentum  and  be  turned  up- 
wards. It  is  then  seen  as  a  long,  pinkish,  cream-coloured 
gland,  stretching  transversely  across  the  posterior  abdom- 
inal wall,  from  the  concavity  of  the  duodenum  to  the 
lower  and  inner  border  of  the  spleen.  In  the  fresh  condi- 
tion it  has  a  firm  consistency  and  a  markedly  lobulated 
appearance.  In  length  it  varies  from  5  to  6  inches  (12  to 
15  cm.).  Its  average  weight  ranges  from  2.25  to  3.5 
ounces  (66  to  102  grams) .  The  general  shape  of  the  gland 
is  aptly  compared  by  Birmingham,  in  Cunningham's 
"  Text-Book  of  Anatomy,"  to  the  letter  J  placed  upon  its 
side,  rH  ,  the  loop  being  thickened  to  represent  the  head, 
the  thickened  stem  corresponding  to  the  body,  and  the 
narrow  bend  joining  the  two  indicating  the  neck. 

The  enlarged  right  extremity,  or  "head,"  extends  down- 
wards and  to  the  left,  lying  in  the  concavity  of  the  duode- 
num in  contact  with  its  second  and  third  parts,  and  oppo- 
site to  the  second  and,  upper  part  of,  the  third  lumbar 
vertebra.  The  short  and  comparatively  narrow  portion 
of  the  gland  termed  the  "neck"  arises  from  the  upper 
and  right  part  of  the  head.  It  runs  upwards  and  to 
the  left,  and,  after  a  course  of  about  one  inch,  merges 
into  the  "body."  This,  which  is  the  longest  section  of 
the  gland,  runs  backwards  and  to  the  left  at  the  level  of 

28 


Fig.  10. — Relations  of  the  pancreas  (Sobotta  and  McMurrich). 


Anatomy 


29 


the  first  lumbar  vertebra.  The  pointed  left  extremity, 
or  "tail,"  is  the  least  firmly  attached  portion  of  the  organ. 
It  merges  so  gradually  into  the  body  that  no  sharp  line  of 
distinction  can  be  drawn  between  the  two. 

The  disc-shaped  head  is  flattened  from  before  back- 
wards. Its  right  and  lower  borders  are  closely  united  to 
the  duodenum,  one-third  of  the  circumference  of  which 
may  te  enveloped   by  the  gland    substance  in  a  well- 


pig_  ji_ — Transverse  section  of  the  abdomen  at  the  first  lumbar  verte- 
bra, to  show  the  relations  of  the  pancreas  (after  Braune). 


developed  organ.  The  right  half,  above,  is  continued  into 
the  neck.  To  the  left,  it  is  separated  from  the  neck  by  a 
deep  groove,  the  "incisura  pancreatis."  In  this  groove 
lie  the  superior  mesenteric  vessels,  which  are  continued 
over  the  anterior  surface  of  the  head,  near  its  left  border. 
That  portion  of  the  gland  which  lies  to  the  left  of  the  ves- 
sels, along  the  third  part  of  the  duodenum,  is  termed  the 
"uncinate  process,"  and  when,  as  happens  occasionally. 


30         The  Pancreas:  Its  Surgery  and  Pathology 

it  is  separated  from  the  rest,  it  is  known  as  the  "lesser 
pancreas."  The  superior  and  inferior  pancreatico-duode- 
nal  vessels  also  course  over  the  head,  near  its  right  and 
left  borders  respectively,  to  break  up  on  its  anterior  sur- 
face. Above  and  to  the  right,  the  anterior  aspect  of  the 
head  is  in  contact  with  the  commencement  of  the  trans- 
verse colon,  the  posterior  surface  of  which  is  directly 
attached  to  the  pancreas  by  areolar  tissue.  The  lower 
part  of  the  anterior  surface  of  the  head  of  the  gland  is 
covered  by  peritoneum,  reflected  from  the  lower  surface 
of  the  colon  and  entering  into  the  formation  of  the  greater 
sac.  This  part  is  in  contact  with  portions  of  the  small 
intestine. 

The  posterior  surface  of  the  head  is  devoid  of  perito- 
neum, and  is  directly  applied  to  the  front  of  the  inferior 
vena  cava,  the  left  renal  vein,  and  the  aorta.  The  com- 
mon bile-duct  also  lies  in  a  groove,  or  canal,  in  this  surface. 

The  neck  springs  from  the  upper  border  of  the  anterior 
surface  of  the  head.  It  passes  slightly  upwards,  forwards, 
and  to  the  left,  to  join  the  body.  It  is  rarely  more  than 
an  inch  (25  mm.)  long,  is  usually  about  0.75  inch  (18  mm.) 
wide,  and  less  than  0.5  inch  (12.8  mm.)  thick.  Its  junc- 
tion with  the  anterior  surface  of  the  head  is  generally 
grooved  by  the  gastro-duodenal  and  superior  pancreatico- 
duodenal arteries  on  the  right  side.  Anteriorly,  and  to 
the  right,  it  is  in  contact  with  the  first  part  of  the  duode- 
num, and  also  with  the  pylorus  when  the  stomach  is 
distended.  Behind,  and  to  the  left,  is  a  groove  in  which 
lie  the  terminations  of  the  superior  mesenteric  and  splenic 
veins  to  form  the  portal  vein. 

The  body  and  tail  together  measure  about  4  to  5  inches 
(10  to  14  cm.).  They  are  of  a  pyramidal  shape  and  pre- 
sent three  surfaces  of  about  equal  width,  averaging  1.25 
inches  (31  mm.). 

The  body  runs  from  right  to  left,  and  slightly  upwards. 
It  is  moulded  to  the  adjacent  organs,  and  is  thickest  in 


Anatomy 


31 


front  of  the  left  kidney.     The  anterior  surface  is  concave, 
and  looks  upwards  and  forwards.     It  is  separated  from 


Fig.  12. — Vertical  section  of  the  body  at  full  term,  showing  the  relation 
of  the  uterus  to  the  pancreas  (after  Braune). 


the  stomach  by  the  lesser  sac  of  the  peritoneum,  the 
posterior  wall  of  which  is  intimately  attached  to  it.     At 


32         The  Pancreas:  Its  Surgery  and  Pathology 

the  right  extremity  of  the  anterior  surface,  where  the 
body  joins  the  neck,  there  is  often  a  well-marked  promi- 
nence, the  "omental  tuberosity,"  so  called  from  its  com- 
ing into  contact  with  the  small  omentum  when  the  stom- 
ach is  distended.  The  posterior  surface  looks  directly 
back,  and  lies  upon  the  aorta,  the  origin  of  the  superior 
tnesenteric  artery,  the  pillars  of  the  diaphragm,  the  splenic 
artery  and  vein  (which  run  a  tortuous  course  along  its 
upper  border  in  a  single  channel  or  may  be  two  separate 
grooves),  the  left  kidney  and  renal  vessels,  and  the  left 
suprarenal  capsule.  This  surface,  like  the  posterior  aspect 
of  the  head,  is  devoid  of  a  peritoneal  covering,  and  is 
connected  to  the  abdominal  wall  and  adjacent  organs 
by  areolar  tissue.  The  inferior  surface  looks  downward 
and  slightly  forward.  It  is  narrowest  at  the  right  end, 
which  rests  upon  the  duodeno- jejunal  flexure,  but  widens 
towards  the  left  extremity,  where  it  comes  into  contact 
with  the  splenic  flexure  of  the  colon.  At  the  full  term  of 
pregnancy  the  uterus  rises  and  comes  into  contact  with 
the  lower  border.  The  middle  portion  is  covered  by  the 
jejunum.  The  whole  surface  is  completely  invested  by 
peritoneum,  derived  from  the  descending  layer  of  the 
transverse  mesocolon. 

The  tail  turns  sharply  upwards,  and  backwards.  As  a 
rule,  it  comes  into  contact  with  the  lower  part  of  the  inner 
surface  of  the  spleen,  but  occasionally  it  is  separated  by  a 
portion  of  mesentery  containing  a  lymph  nodule. 

The  blood-supply  of  the  body  and  tail  of  the  pancreas 
is  mainly  derived  from  the  splenic  artery.  The  hepatic 
division  of  the  coeliac  axis  and  the  inferior  pancreatico- 
duodenal branch  of  the  superior  mesenteric  supply  chiefly 
the  head.  The  superior  (anterior)  pancreatico-duodenal 
artery  is  a  branch  of  the  gastro-duodenal ;  passing  on  to 
the  front  of  the  head,  it  sends  branches  into  the  sub- 
stance, and  also  on  to  the  duodenum.  The  inferior 
(posterior)   pancreatico-duodenal  artery  arises  from  the 


Anatomy 


33 


upper  part  of  the  superior  mesenteric,  or  occasionally 
from  the  middle  colic,  artery;  it  passes  upward,  and  to 
the  right,  across  the  back  of  the  head,  and  sends  branches 
to  it  and  to  the  neighbouring  duodenum.  The  two  pan- 
creatico-duodenal  vessels  frequently  anastomose  around 
the  lower  border  of  the  head  of  the  pancreas  and  form  a 
vascular  loop.     The   inferior   pancreatic  branch   of  the 


Fig.  13. — Arteries  and  veins  of  the  pancreas. 


superior  mesenteric  artery  runs  to  the  left,  along  the  lower 
border  of  the  pancreas,  often  as  far  as  the  tail.  A  large 
number  of  small  branches  are  given  off  by  the  splenic 
artery  to  the  body  and  tail  as  it  courses  along  the  upper 
border  of  the  gland.  Small  pancreatic  branches  are  also 
given  off  by  the  hepatic  artery  as  it  rests  upon  the  upper 
border. 
3 


34         The  Pancreas:  Its  Surgery  and  Pathology 

The  veins  are  all  tributaries  of  the  splenic  and  superior 
mesenteric,  the  blood  from  the  pancreas  being  thus  car- 
ried to  the  portal  system.  The  anterior  (superior)  pan- 
creatico-duodenal  vein  lies  on  the  front  of  the  head,  and 
joins  the  superior  mesenteric.  The  posterior  pancreatico- 
duodenal runs  on  the  back  of  the  head  to  open  into  the 
portal  vein.  A  number  of  small  tributaries  of  the  splenic 
vein,   corresponding  to  the   arterial  branches  from  the 


Gastrohepatic  omentum. 


Aorta. 


Tuber  omentale. 


Layers  of 
transverse 
mesocolon. 


Colon 


Uncinate  process. 


Mesentery. 
Mesenteric  artery  and  vein. 


Fig.  14. — Peritoneal  reflexions  on  the  pancreas  (after  Testut). 


splenic  artery,  collect  the  blood  from  the  body  of  the 
gland.  There  are  also  many  small  veins  arising  in  the 
head  and  neck  which  run  into  the  portal  vein. 

There  is  a  complex  network  of  lymphatic  vessels  in  and 
around  the  gland,  which  opens  into  glands  situated  on 
the  head  of  the  pancreas,  in  the  hilum  of  the  spleen,  and 
along  the  superior  mesenteric  vessels. 

The  nerves  of  the  pancreas  are  provided  by  cerebro- 
spinal   fibres   coming   from   the   vagi,    and   sympathetic 


Anatomy  05 

fibres  derived  from  the  solar  plexus.  They  accompany 
the  arteries  through  the  coeliac,  splenic,  and  superior 
mesenteric  plexuses,  and,  travelling  in  the  substance  of 
the  gland  with  the  ducts,  terminate  round  the  acini  in 
rich  plexuses  of  fibres  which  send  fibres  to  the  secreting 
cells  (Miiller) .  The  nerve  fibres  are  almost  entirely  non- 
medullated  and  have  minute  ganglia  on  them  (visceral 
sympathetic  ganglia  cells— R.  y  Cajal)  as  they 
traverse  the  gland,  and  near  their  dis- 
tribution to  the  alveoli  small  cells,  ap- 
parently of  a  nervous  nature, 
are  also  found. 


Common  bile- 
duct. 

Duct  of  San- 
torini. 
Orifice  of  the 
duct  of  Santorini. 
Orificeof  the  duct 
of  Wirsungand 
the   common 
bile-duct. 


Duct  of  Wirsung. 
Fig.  15. — The  excretory  ducts  of  the  pancreas  (after  Testut). 

Peritoneum. — The  transverse  mesocolon  is  attached  to 
a  line  running  along  the  anterior  border  of  the  pancreas 
from  the  neck  to  the  tail.  The  anterior  layer  passes 
upwards  and  backwards,  over  the  superior  surface,  to 
form  the  posterior  wall  of  the  lesser  sac,  the  posterior 
going  downwards  and  backwards,  along  the  inferior  sur- 
face to  form  the  greater  sac.  At  the  neck,  and  on  the 
head,  the  two  sheets  of  peritoneum  have  separate  lines  of 
attachment,  so  that  a  somewhat  variable  area  is  devoid 
of  a  peritoneal  covering  and  is  only  separated  from  the 
colon  by  areolar  tissue.     In  many  cases,  however,  the 


36         The  Pancreas:  Its  Surgery  and  Pathology 


transverse  mesocolon  is  continued  as  far  as  the  hepatic 
flexure,  so  that  the  head  and  neck  receive  a  complete 
peritoneal  investment.    The  posterior 
surface  is  quite  uncovered  by  perito- 
neum. 

Ducts. — The  pancreas  has  normally 
two  ducts  which  open  separately  into 
the  duodenum.  The  main  duct,  or 
duct  of  Wirsung,  commences  in  the 
tail  by  the  union  of  the  small  tribu- 
taries draining  that  region,  and  grad- 
ually increases  in  size  as  it  courses 
through  the  body  of  the  gland  from 
left  to  right.  In  the  neck  it  alters 
its  course,  bending  downwards  and 
backwards,  to  reach  the  head  of  the 
organ.  In  the  latter  it  lies  nearer  the 
posterior  than  the  anterior  surface, 
and  comes  into  relation  with  the 
common  bile-duct,  beside  which  it 
runs  to  the  duodenum.  The  two 
ducts  pierce  the  wall  of  the  second 
part  of  the  duodenum  obliquely, 
about  3  to  4  inches  (8  to  12  cm.) 
below  the  pylorus,  to  open  into  the 
lumen  of  the  gut  by  a  common  ori- 
fice, situated  on  a  papilla-like  fold 
of  the  mucous  membrane  called  the 
' '  papilla  or  caruncula  major. ' '  Above 
this  there  is  constantly  found  a  small 
fold  of  mucous  membrane,  which 
must  be  raised  in  order  that  the 
caruncle  and  its  orifice  may  be  seen, 
and  running  downwards  from  the 
caruncle  is  a  small  vertical  fold  known  as  the  "frenum 
carunculas"  or  "plica  longitudinalis. ' '    Shortly  before  their 


Fig.  16. — Photo- 
graph of  a  specimen 
in  the  Hunterian 
Museum  of  the  Royal 
College  of  Surgeons, 
showing  the  separate 
lobules  of  the  pan- 
creas with  their 
ducts  opening  into 
the  duct  of  Wirsung 
(anatomical  series 
277). 


Anatomv 


37 


termination  the  common  bile-duct  and  pancreatic  duct 
usually  unite  to  form  a  common  channel,  known  as  the 
"  ampulla  or  diverticulum  of  Vater. ' '  This  is  a  small  oval 
or  triangular  cavity  lying  in  the  wall  of  the  duodenum, 
having  its  apex  at  the  duodenal  orifice,  and  its  base  at 
the    openings   of   the   two   ducts.     Its   average   length, 


Neck  of  gall-bladder 

and  cystic  duct.       Hepatic  duct.        Portal  vein. 


Common  bile 
duct. 


Duoden 


Hepatic  artery 


Head  of  pan 
creas. 


Uncinate  process. 


Superior  mesenteric  artery  and  vein. 

Fig.  17. — Head  and  neck  of  the  pancreas,  viewed  from  the  front  (after 

Testut). 


according  to  Opie,  is  3.9  mm.  Occasionally  it  may  be  as 
long  as  II  mm.,  while  in  other  cases  it  is  non-existent, 
the  two  ducts  opening  side  by  side  upon  the  common 
papilla.  The  orifice  of  the  common  bile-duct  into  the 
ampulla  is  above  that  of  the  pancreatic  duct,  and  the 
two  are  separated  by  a  small  transverse  fold  of  mucous 


38         The  Pancreas:  Its  Surgery  and  Pathology 

membrane.  The  average  diameter  of  the  duodenal  open- 
ing of  the  ampulla,  which  is  always  the  narrowest  part  of 
the  bile  channel,  is  2.5  mm.  (Opie),  but  in  some  instances 
it  is  equal  to,  or  greater  than,  the  length  of  the  divertic- 
ulum. The  ampulla,  and  the  terminations  of  the  two 
ducts,  are  surrounded  by  a  thin  layer  of  unstriped  muscle 
fibre,  forming  a  sphincter  (Oddi) . 


Fig.  18. — Preparation  showing  the  common  bile-duct  and  pan- 
creatic ducts  and  their  common  point  of  entry  into  the  duodenum 
(Royal  College  of  Surgeons  Museum,  anat.  series  275  B). 


The  accessory  duct,  or  duct  of  Santorini,  is  a  very 
variable  structure.  For  a  long  time  it  was  regarded  as 
inconstant,  but  more  extended  and  thorough  investiga- 
tion has  shown  that  it  is  always  present,  although,  at 
times,  it  is  small,  or  partly  obliterated,  especially  in  the 
neighbourhood  of  the  intestine.  Opie  in  the  examination 
of  100  bodies  found  that  the  duodenal  orifice  of  the  lesser 


Anatomy 


39 


duct  was  obliterated,  or  so  constricted  as  to  be  of  little 
or  no  functional  service,  in  over  half  the   cases  investi- 


Common  bile-duct. 


Valvula;  coiiiii 
ventes. 


of  Vater. 
carunculae. 


Fig.  19. — Diagram  showing  the  formation  of  the  ampulla  of  Vater 
by  the  union  of  the  common  bile-duct  and  pancreatic  duct  and  their 
opening  into  the  duodenum  (after  Testut). 


Caruncula  major. 


Frenum  carunculae. 


Fig.  20. — Opening  of  the  ampulla  of  Vater  on  the  caruncula  major  in 
the  duodenum  (after  Testut). 


gated.     The  opening,  when  present,  is  situated  on  a  small 
papilla,  "the  papilla  or  caruncula  minor,"  lying  0.75  to  i 


40         The  Pancreas:  Its  Surgery  and  Pathology 

inch  above,  and  somewhat  ventral  to,  the  papilla  major 
on  which  the  ampulla  of  Vater  or  the  main  duct  opens. 
The  duct  of  Santorini  is  morphologically,  and,  in  some 
instances,  anatomically,  the  duct  of  the  head  of  the  pan- 
creas, representing  what,  in  the  lower  vertebrates,  is  the 
excretory  duct  of  the  duodenal  portion  of  the  organ.  In 
man,  as  in  many  mammals,  the  main  and  accessory  ducts 
communicate  with  each  other  within  the  gland  by  branches 
of  varying  size. 

Literature 

Birmingham:  Cunningham.'s"  Text -book  of  Anatomy,"  1906. 

Cajal,  R.  y. :    "Terminacion  de    los  nervos  y  tubos  glandulaires   del 

pancreas  de  los  vertebrados,"  Barcelona,  1891. 
Miiller:  Archiv.  f.  mile.  Anat.,  xi,  405,  1892. 
Schafer  and  Symington:  Quain's  "Anatomy,"  iii,  Part  4. 
Testut:    "Traite  de  Anatomic  humaine,"  viii,  1894. 


CHAPTER  III 

EMBRYOLOGY 

It  was  formerly  taught  that  the  pancreas  arises  in  verte- 
brates by  two  outgrowths  from  the  walls  of  the  duodenum, 
the  one  dorsal  and  the  other  ventral,  but  it  has  now  been 
shown,  for  most  members  of  the  group,  including  man, 
that  the  ventral  bud  in  its  early  stages  is  double,  so  that 


Liver 


Gall-bladder 


Common  bile- 
duct 


Duodenum 


Stomach 


Dorsal  pancreatic 
bud 


Ventral  pancreatic  bud 


Fig.  21. — The  pancreatic  and  hepatic  processes  of  a  fourth-week  em- 
bryo (after  Kollmann). 

a  triple  origin  of  the  primitive  rudiment,  or  anlage,  of 
the  pancreas  is  now  generally  accepted. 

The  first  indication  of  the  pancreas  in  man  is  seen  in 
the  fourth  week  of  intrauterine  life,  as  a  process  from  the 
dorsal  wall  of  what  will  later  become  the  second  part  of 
the  duodenum.  It  grows  out  between  the  layers  of  the 
dorsal  mesogastrium  and  eventually  reaches  the  spleen, 

41 


42         The  Pancreas:  Its  Surgery  and  Pathology 

as  it  lies  above  the  cardiac  end  of  the  stomach.  From 
the  opposite  wall  of  the  duodenum  the  two  ventral  buds 
take  their  origin,  on  either  side  of  the  hepatic  diverticu- 
lum, which  has  made  its  appearance  at  an  earlier  date. 
As  they  increase  in  size  they  fuse  together  to  form  a  sin- 
gle mass,  which  later  unites  with  the  larger  dorsal  out- 


Gastrohepatic 
omentum 


Spleen 

Dorsal  meso- 
gastrium 
—  Stomach 


Mesentery 


// 


Fig.  2  2. — The  relation  of  the  pancreas,  spleen,  and  liver  to  the  xneso- 
gastrium  in  the  embryo  (after  Keith). 


growth.  The  greater  part  of  the  adult  pancreas  is  de- 
rived from  the  dorsal  process,  the  ventral  buds  only 
giving  rise  to  the  lower  part  of  the  head  (Fig.  23). 

Originally,  the  gland  lies  parallel  to  the  dorsal  border 
of  the  stomach,  the  head  occupying  the  bend  of  the  duo- 
denal loop  and  the  tail  being  directed  forwards  against 
the  spleen.     The  whole  gland  is  then  completely  invested 


Embryology 


43 


with  peritoneum.  As  the  stomach  rotates  to  the  left, 
and  the  great  omentum  is  developed,  the  pancreas  comes 
to  lie  transversely  across  the  abdominal  cavity.  The 
former  right  surface  now  becomes  posterior,  and  is  closely 
applied  to  the  wall  of  the  abdomen.  Its  peritoneal  cover- 
ing gradually  disappears  and  is  replaced  by  a  connecting 
layer  of  areolar  tissue.  The  anterior  aspect  of  the  gland, 
which  was  formerly  its  left  surface,  comes  to  lie  behind 


Dorsal 
Gastrohepatic  mesentery 

omentum 


Common 
bile-ducl 


"~  Pancreas 


Mesentery 


Duct  of 

Wirsung 


Duodenum 


Ventral  pancreas 

Fig.  23. — Diagram  of  the  pancreas  showing  its  relation  to  the 
dorsal  and  ventral  mesenteries,  the  parts  formed  from  the  ventral  and 
dorsal  outgrowths ;  and  the  formation  of  the  duct  of  Wirsung  by  a 
union  between  the  ducts  of  the  dorsal  and  ventral  buds  (after  Keith). 


the  stomach  and  retains  its  peritoneal  coat,  so  that  the 
adult  arrangement  of  the  pancreas,  outside  the  peritoneal 
cavity,  is  reached.  In  many  animals  a  process  from  the 
dorsal  outgrowth  extends  into  the  gastro-hepatic  omen- 
tum as  an  omental  lobe,  and,  in  man,  this  is  sometimes 
found  to  be  represented  by  a  well-marked  omental  tuber- 
osity. 

Each  primitive  pancreatic  outgrowth  is  provided  with  a 


44         The  Pancreas:  Its  Surgery  and  Pathology 

duct  opening  into  the  duodenum.  That  from  the  ven- 
tral process  opens  by  an  orifice  common  to  it  and  the 
hepatic  diverticulum,  close  to  which  it  originated.  The 
duct  of  the  dorsal  bud  communicates  with  the  duodenum 
by  an  opening  situated  nearer  to  the  pylorus.  The  two 
ducts  almost  always  anastomose  within  the  substance  of 
•the  gland  at  an  early  stage,  and  it  is  found  that,  as  a  con- 
sequence of  this,  the  chief  excretory  channels  of  the  adult 
pancreas  are  usually  of  complex  origin.  The  main  duct, 
or  duct  of  Wirsung,  of  the  adult  is  partly  derived  from  the 
duct  of  the  dorsal  process  and  partly  from  that  of  the 
ventral  outgrowth.  That  part  which  lies  in  the  body  of 
the  gland  represents  the  main  portion  of  the  dorsal  em- 
bryonic duct,  and  that  which  courses  through  the  head, 
opening  into  the  duodenum  along  with  the  common  bile- 
duct,  is  derived  from  part  of  the  dilated  channel  of  the 
ventral  pancreatic  process.  The  remaining  section  of  the 
dorsal  duct,  lying  between  the  point  of  anastomosis  of 
the  two  primitive  channels  and  the  duodenal  opening, 
usually  undergoes  partial  atrophy  and  becomes  the  acces- 
sory pancreatic  duct,  or  duct  of  Santorini,  of  the  adult 
organ. 

The  primary  pancreatic  processes  are  hollow,  but  the 
secondary,  tertiary,  and  succeeding  buds  which  arise 
from  their  walls  consist  of  solid  masses  of  cells.  Later 
these  acquire  a  lumen  and  the  typical  structure  of  the 
acinotubular  pancreas  is  gradually  developed. 

Literature 

Brachet:   Journ.  de  I'Anat.  et  de  la  Phys.,  1896,  xxxii,  620. 
Brunn,  Von:    Merkel-Bonnet  Ergebnisse,  1894,  Abt.  ii,  iv,  87. 
Choronschizky :    Ref.,  Anat.   Hefte,  Merkel-Bonnet,  Ergebnisse,  1899, 

Abt.  ii,  ix,  669. 
Felix:  Arch.  f.  Anat.  u.  Phys.,  1892,  Anat.  Abt.,  281. 
GSppert:    Morphol.  Jahrb.,  1891,  xvii,  100. 
Gotte:   Leipzig,  1875. 

Hamburger:    Anat.  Anzeiger,  1892,  vii,  707. 
Hammar:   Arch.  f.  Anat.  u.  Phys.,  Anat.  Abt.,  1893,  123. 
Helly:  Arch.  f.  mik.  Anat.,  1900,  Ivi,  291;    1901,  Ivii,  271. 
Jankelowitz:    Inaug.  Diss.,  Berlin,  1895. 


Embryology  45 

Keith:   "Human  Embryology  and  Morphology,  "  1904. 

Laguesse:   Bibliogr.  Anat.,  1894.,  ii,  loi. 

Opie:    "Diseases  of  the  Pancreas,"  1903. 

Schafer:    Quain's  "Anatomy,"  1896. 

St5hr:  Anat.  Anzeiger,  1893,  viii,  205. 

Stoss:  Anat.  Anzeiger,  1891,  vi,  666. 

V5lker:   Arch.  f.  mik.  Anat.,  1902,  lix,  62. 

Wlassow:   Morpholog.  Arbeiten  herausgeg.  von  Schwalbe,  189';  iv,  67. 

Zimmermann:   Anat.  Anzeiger,  1889,  iv,  139. 


CHAPTER  IV 
ANATOMICAL  ANOMALIES 

When  considering  the  anatomical  anomaHes  of  the  pan- 
creas it  is  important  that  the  embryology  and  compara- 
tive anatomy  of  the  organ  should  be  borne  in  mind,  for 
by  this  means  arrangements  and  distributions  of  the 
glandular  substance,  which  would  otherwise  appear  cap- 
ricious, are  explained,  and  abnormalities  of  the  ducts  are 
simplified. 

The  abnormality  around  which  most  of  the  literature 
of  the  subject  centres,  and  which  has  aroused  the  greatest 
amount  of  controversy,  is  the  occurrence,  in  from  0.5  to 
I  per  cent,  of  persons,  of  one  or  more  accessory  masses  of 
glandular  tissue.  These  accessory  pancreases  have  been 
classified  by  Glinski  into  three  divisions : 

1.  ''Pancreas  minus,''  in  which  a  supernumerary  lobule, 
or  lobe,  is  present  in  the  head  of  the  gland,  separated  by 
a  more  or  less  marked  constriction. 

2.  ''Pancreas  accessorium,"  where  isolated  nodules  of 
pancreatic  tissue  are  found  embedded  in  the  walls  of  the 
gastro-intestinal  tract,  or  in  other  situations. 

3.  "Pancreas  divisum,"  in  which  parts  of  the  gland 
may  be  found  separated  from  the  main  mass,  but  still 
connected  by  means  of  their  ducts  to  the  chief  excretory 
channel  of  the  organ. 

Pancreas  Minus. — Examples  of  the  first  variety  can 
hardly  be  classed  as  instances  of  an  accessory  pancreas, 
for  they  only  represent,  as  a  rule,  an  exaggeration  of  a 
normal  condition,  in  which  a  portion  of  the  pancreas  is 
separated  from  the  remainder  by  a  more  marked  depres- 
sion than  usual. 

46 


Anatomical  Anomalies  47 

The  commonest  is  that  to  which  reference  has  already 
been  made  when  considering  the  anatomy  of  the  gland. 
In  this  variety  a  portion  of  the  head,  lying  behind  the 
mesenteric  vessels,  is  divided  from  the  rest  by  a  deep 
cleft  to  form  the  lesser  pancreas  ("pancreas  parvum"  of 
Winslow).  Occasionally,  however,  the  cleft,  in  which 
the  superior  mesenteric  vessels  lie,  is  bridged  over  so 
that  they  are  contained  in  a  canal  in  the  head  of  the  pan- 
creas, and  the  descending  lobe  is  thus  firmly  fixed  to  the 
body. 

A  rarer  anomaly,  of  much  surgical  interest,  is  an  exag- 
geration of  another  normal  condition.  It  has  already 
been  pointed  out  that  the  head  of  a  w^ell-developed  gland 
may  embrace  one-third  of  the  circumference  of  the  second 
part  of  the  duodenum ;  in  rare  cases  the  overlapping  is  so 
great  that  the  whole  circumference  of  the  bowel  is  en- 
closed in  a  ring  of  pancreatic  tissue.  Either  at  birth,  or 
later  if  the  gland  should  be  invaded  by  growth  or  become 
enlarged  from  inflammatory  changes,  it  may  lead  to 
symptoms  of  obstruction  resembling  those  due  to  pyloric 
stenosis.  Shirmer  collected  four  examples  of  this  con- 
dition from  the  older  literature,  quoting  cases  by  Tiede- 
mann,  Becourt,  Moyse,  and  Ecker.  More  recently  in- 
stances have  been  recorded  by  Symington,  Generisch, 
Tieken,  Santos,  and  Vidal.  That  of  the  last  named  was 
in  a  child,  and  the  symptoms,  which  appeared  immediately 
after  birth,  suggested  congenital  stenosis  of  the  pylorus. 
At  operation  the  true  state  of  things  was  discovered,  and 
gastro-enterostomy  was  performed  to  relieve  the  ob- 
struction. The  patient  recovered  and  steadily  gained  in 
weight  after  the  operation.  The  case  operated  on  by  Santos 
was  a  woman  of  twenty-six,  who  sufTered  from  constant 
vomiting  and  was  much  emaciated.  Gastro-enterostomy 
was  performed,  but  the  patient  died  and  the  anomaly 
of  the  pancreas  was  confirmed  post-mortem  (Fig.  24), 
Symington's  case  was  discovered  post-mortem  in  an  adult 


48         The  Pancreas:  Its  Surgery  and  Pathology 

male,  and  is  described  as  follows  in  the  "Journal  of  Anat- 
omy and  Physiology"  for  1885:  "On  distending  the 
intestine  with  air,  in  order  to  facilitate  the  dissection  of 
the  head  of  the  pancreas,  it  was  noticed  that  the  upper 
part  of  the  descending  portion  did  not  become  dilated 
like  the  rest  of  the  intestine,  and  on  examination  this 
was  found  to  be  due  to  its  being  completely  surrounded 
in  that  situation  by  pancreatic  tissue.  Two  processes  of 
the  pancreas  passed  from  the  upper  part  of  the  head  of 


Fig.  24. — Congenital  malformation  of  pancreas  compressing  the 
duodenum  and  leading  to  obstruction  which  required  gastro-enter- 
ostomy.  Stomach  and  duodenum  laid  open,  showing  the  gastro- 
enterostomy opening  and  the  stricture  caused  by  the  pancreas  (Santos). 

the  gland  towards  the  right,  one  in  front  and  the  other 
behind  the  duodenum.  They  blended  on  its  outer  side 
so  as  to  form,  with  the  head  of  the  gland,  a  ring  of  pan- 
creas encircling  the  duodenum.  The  processes  became 
somewhat  narrower  as  they  passed  outwards,  and  the 
portion  of  the  gland  on  the  right  side  of  the  duodenum 
was  about  half  an  inch  in  vertical  extent.  On  dissecting 
out  the  ducts  of  the  pancreas  nothing  unusual  was  ob- 
served  in   their   arrangement.     The    common   bile-duct 


Anatomical  Anomalies  49 

opened  into  the  duodenum  below  the  seat  of  the  constric- 
tion. The  circumference  of  the  distended  duodenum, 
where  it  was  surrounded  by  the  pancreas,  was  two  and  a 
half  inches,  while  above  and  below  that  it  was  more  than 
three  times  as  large.  In  a  case  operated  on  by  one  of  us, 
a  prolongation  from  the  head  of  the  pancreas  was  found 
extending  upwards,  in  front  of  the  common  bile-duct  and 
the  hepatic  duct,  and  exerting  pressure  on  both,  owing 
to  its  being  inflamed  and  swollen. 

The  body  and  tail  of  the  pancreas  are  rarely  the  seat 
of  anatomical  abnormalities.  Occasionally  the  latter  is 
bifid,  and  a  case  has  been  recorded  by  Klobin  in  which 
an  enlargement  of  the  tail  was  found  on  investigation  to 
contain  an  accessory  spleen. 

Glinski's  third  division,  "pancreas  divisum,"  also 
hardly  merits  the  description  of  accessory  pancreas,  for 
it  is  really  represented  by  portions  of  the  gland  which 
have  become  separated  by  the  mechanical  pressure  of 
blood-vessels,  etc.,  during  development.  Hyrtl  has  de- 
scribed cases  belonging  to  this  class  in  which  the  head  of 
the  gland  was  separated  from  the  body,  a  portion  of  the 
head  lay  behind  the  mesenteric  vessels,  and  the  tail  was 
separated  from  the  body  of  the  organ.  Engel  records  an 
instance  in  which  a  portion  of  the  pancreatic  tissue  was 
situated  under  the  head,  and  at  the  inner  side  of  the 
descending  portion  of  the  duodenum,  but  was  connected 
with  the  main  pancreatic  duct. 

Pancreas  Accessorium. — The  condition  to  which  the 
term  "accessory  pancreas"  strictly  applies,  and  which 
most  writers  describe  under  that  name,  is  the  occurrence 
in  connection  with  some  part  of  the  gastro-intestinal  tract 
of  one  or  more  masses  of  pancreatic  tissue  in  an  abnormal 
situation  and  independent  of  the  main  mass  of  the  gland. 
It  is  this  which  forms  the  second  division  of  Glinski's 
classification,  the  "pancreas  accessorium."  Accessory 
masses  of  pancreatic  tissue  have  been  described  in  the 


50         The  Pancreas:  Its  Surgery  and  Pathology 


walls  of  the  stomach,  duodenum,  jejunum,  and  ileum. 
Thorel  has  maintained  that  they  are  most  commonly  met 
with  in  the  stomach,  but  Glinski  states  that  the  intestinal 
wall  is  the  more  frequent  site.  A  survey  of  the  literature 
of  the  subject  tends  to  support  Glinski 's  contention. 

We  have  been  able  to  meet  with  records  of  thirty-seven 
cases,  in  which  forty-one  masses  of  accessory  pancreatic 
tissue  were  present,  and  to  these  we  have  to  add  the 
hitherto  unpublished   specimen  shown  in  Fig.  25,  from 

the  Leeds  Pathological  Museum. 
It  was  discovered  at  a  post- 
mortem examination  made  by 
W.  H.  Maxwell  Telling  and  was 
situated  in  the  wall  of  the  in- 
testine at  the  duodeno- jejunal 
junction.  In  eight  instances 
(Klob,  Gegenbaur,  Weichsel- 
baum,  Glinski,  Schirmer,  and 
three  by  Opie)  there  was  a  sin- 
gle nodule  in  the  wall  of  the 
stomach.  In  one,  recorded  by 
Opie,  there  was  a  mass  of  pan- 
creatic tissue  in  the  stomach 
wall,  8  cm.  from  the  pylorus, 
and  a  second  mass  at  the  py- 
lorus, which  on  microscopical 
examination  was  only  found  to  contain  a  dilated  duct. 
Opie  also  describes  a  case  in  which  an  accessory  pancreas 
was  found  in  the  stomach,  2  mm.  from  the  pylorus,  and 
another  nodule  in  the  wall  of  the  duodenum,  9.5  cm. 
below  the  pylorus.  Wagner  records  an  instance  where  an 
accessory  pancreas  was  present  on  the  anterior  wall  of  the 
stomach,  midway  between  the  pylorus  and  the  cardiac 
end,  and  a  second  nodule,  the  exact  situation  of  which 
is  not  described,  in  the  intestine. 

Twenty-nine    accessory    masses    of    pancreatic    tissue 


E.n-WRlCjHTr 


Fi^:.  25.  —  Accessory 
pancreatic  nodule  in  the 
intestinal  wall  at  the  duo- 
den  o-jejunal  junction. 


Anatomical  Anomalies  51 

have  been  described  in  the  intestine ;  all,  however,  were 
situated  above  the  ileo-ca;cal  valve.  Six  were  met  with 
in  the  walls  of  the  duodenum  (Weichselbaum,  Zenker, 
and  four  by  Opie).  One  of  Opie's  cases  has  already  been 
referred  to  in  connection  with  a  similar  nodule  in  the 
stomach.  Four  lay  in  the  wall  of  the  duodenum  above 
the  pancreas,  one  was  situated  on  the  convex  border 
opposite  the  head  of  the  gland  (Zenker),  and  one  was 
below  the  pancreas  (Opie).  The  nodule  in  Telling's  case 
lay  at  the  duodeno- jejunal  junction. 

We  have  been  able  to  find  records  of  nine  cases  in 
which  a  single  mass  of  pancreatic  tissue  was  present  in 
the  wall  of  the  jejunum  (Klob,  Turner,  Xicholls,  Lewis, 
Zenker  three,  and  Opie  two).  In  all  but  one  case  it  lay 
within  two  or  three  feet  of  the  origin  of  the  gut.  The 
exception  is  described  by  Opie,  and  here  it  was  situated 
4  metres  from  the  stomach.  Zenker  quotes  a  case  in 
which  two  accessory  pancreases  were  present  in  the  jeju- 
nal walls,  one  16  cm.  below  the  duodenum,  and  the  second 
32  cm.  lower  down. 

The  five  cases  in  which  an  accessory  pancreas  was  found 
associated  with  the  ileum  are  peculiar  in  that  the  glandu- 
lar tissue  was  in  each  instance  situated  at  the  end  of  a 
slender  or  funnel-shaped  diverticulum  of  the  intestinal 
wall  (Zenker,  Neumann,  Nauwerck,  Hansemann,  Schirmer) . 

This  peculiarity  is  not,  however,  confined  to  the  ileum, 
for  in  Weichselbaum 's  case  of  an  accessory  pancreas  in 
the  stomach  wall  the  nodule  was  situated  at  the  bottom 
of  a  diverticulum  near  the  pylorus,  and  in  cases  described 
by  Roth,  Opie,  and  RoUeston  diverticula  were  found  on 
the  left  side  of  the  duodenum,  running  into  the  substance 
of  the  pancreas.  The  fact  that  the  ileal  outgrowths  have 
been  most  commonly  found  about  two  feet  from  the  ileo- 
cascal  valve  has  naturally  suggested  that  they  were  the 
remains  of  the  vitelline  duct  and  examples  of  Meckel's 
diverticulum.     The  occurrence  of  similar  csecal  appen- 


52         The  Pancreas:  Its  Surgery  and  Pathology 

dages  apart  from,  and  in  connection  with,  pancreatic 
tissue  in  other  situations  along  the  walls  of  the  gastro- 
intestinal tract,  and  the  fact  that  the  vitelline  duct  is 
already  formed  when  the  pancreas  begins  to  develop, 
are,  however,  opposed  to  such  a  theory.  The  discovery 
of  a  true  Meckel's  diverticulum,  in  addition  to  the  intes- 
tinal outgrowth  containing  pancreatic  tissue,  in  three 
cases  has  cast  further  doubt  on  the  suggestion.  The 
shorter  forms  may  be  possibly  explained  by  the  weaken- 
ing of  the  muscular  wall  of  the  gut,  produced  by  the 
inclusion  of  the  pancreatic  tissue,  which  would  allow 
the  mucous  membrane  to  bulge  outwards  under  the  pres- 
sure of  the  intestinal  contents,  and  to  carry  before  it  the 
pancreatic  nodule  and  remains  of  the  muscular  tissue. 
It  is  more  probable,  however,  that  they  are  the  result  of 
traction  exerted  during  development.  The  similarity, 
at  least  of  the  pyloric  and  duodenal  diverticula,  to  the 
caeca  found  around  the  pylorus  and  along  the  duodenum 
of  some  fishes  raises  the  interesting  question  as  to  whether 
some  of  them  may  not  be  a  partial  reversion  to  an  an- 
cestral type.  A  unique  case  has  been  recorded  by  Wright, 
in  which  a  mass  of  pancreatic  tissue,  3.5  mm.  in  diameter, 
was  found  embedded  in  the  wall  of  a  congenital  umbilical 
fistula,  and  apparently  connected  with  the  persistent  re- 
mains of  the  vitelline  duct. 

Letulle  met  with  five  cases  in  which  an  accessory 
pancreas  was  present  in  two  hundred  post-mortems, 
but  unfortunately  he  gives  no  details.  Opie  collected 
ten  examples  from  eighteen  hundred  autopsies,  which 
have  been  included  in  the  foregoing  survey  of  the  subject. 

The  investigations  of  Helly  have  shown  that  in  many 
individuals  a  small  mass  of  pancreatic  tissue,  forming  a 
true  accessory  pancreas,  lies  in  the  papilla  of  Santorini's 
duct,  entirely  isolated  from  the  remainder  of  the  gland, 
and  either  communicating  directly  with  the  duodenum 
by  a  separate  channel,  or  draining  by  a  small  tributary 


Anatomical  Anomalies  53 

into  the  lesser  duct  near  its  termination.  Opie  has  con- 
firmed these  observations  and  described  a  similar  condi- 
tion in  connection  with  the  duct  of  Wirsung. 

The  accessory  pancreas  in  all  the  recorded  cases,  except 
those  of  Klob  and  Wright,  was  connected  to  the  adjacent 
lumen  of  the  alimentary  tract,  or  diverticulum  from  it, 
by  one  or  more  ducts,  which  in  some  instances  opened  on 
to  a  well-defined  papilla.  In  Klob's  case  it  is  possible 
that  the  duct  was  overlooked. 

The  size  of  the  pancreatic  nodule  varies  considerably 
in  different  cases.  No  exact  measurements  are  given  in 
the  older  records,  but  a  rough  idea  can  be  formed  from 
the  comparison  with  a  bean  and  a  hempseed,  by  Weichsel- 
baum,  and  a  pea  b}^  Neumann.  The  largest  recorded 
accessory  pancreas  is  that  described  by  Glinski,  which 
measured  4.5  by  3.5  by  i.o  cm.  They  are  usually  much 
smaller  than  this,  however,  and  range  about  i.o  cm.  in 
diameter.  The  smallest  is  described  by  Opie,  and 
measured  only  3  mm. 

As  a  rule,  they  lie  embedded  in  the  muscular  tissue  of 
the  gut  wall,  projecting  more  or  less  into  the  submucosa, 
and  beneath  the  peritoneum,  but  occasionally  they  lie  in 
the  submucosa  only. 

Microscopically  these  accessory  nodules  have  the  char- 
acters of  ordinary  pancreatic  tissue.  Islands  of  Langer- 
. hans  were  present  in  cases  described  by  Wright,  Opie, 
and  Lewis,  but  Le tulle  and  Turner  were  unable  to  dis- 
cover them  in  their  cases.  In  many  instances  there  has 
been  an  increase  of  the  interstitial  fibrous  tissue,  indi- 
cating that  the  gland  substance  has  undergone  chronic 
inflammatory  changes,  and  in  some  the  fibrosis  has 
advanced  to  such  a  stage  that  few  or  none  of  the  glandular 
elements  remained.  In  such  cases  the  nodule  may 
present  characters  suggesting  an  adenoma,  or  may  only 
consist  of  fibrous  tissue  with  a  few  dilated  ducts  (Opie). 
It  has  been  suggested  that  the  presence  of  one  or  more 


54         The  Pancreas:  Its  Surgery  and  Pathology 

masses  of  accessory  pancreatic  tissue  in  the  walls  of  the 
gastro-intestinal  tract  may  stay,  or  prevent,  the  onset  of 
diabetes  in  cases  where  the  main  gland  is  diseased,  but, 
when  the  small  size  of  even  the  largest  recorded  examples 
is  taken  into  account,  and  the  frequency  with  which  their 
contained  gland  substance  shows  evidence  of  disease  is 
considered,  it  would  appear  to  be  unlikely  that  they  can 
exert  any  material  influence  in  that  direction. 

There  has  been  much  speculation  as  to  the  origin  of 
these  accessory  pancreatic  nodules.  Zenker  has  explained 
them  by  supposing  that  an  additional  pancreatic  rudi- 
ment occasionally  arises  from  the  duodenum,  close  to  the 
origin  of  the  normal  buds,  and  that,  becoming  attached  to 
the  stomach,  or  duodenum,  as  the  case  may  be,  it  is 
carried  upwards,  or  downwards,  by  the  growth  of  the 
gastro-intestinal  tract,  eventually  becoming  separated 
from  its  origin  to  form  a  distinct  mass  of  pancreatic 
tissue  in  one  or  other  situation.  More  recently  Glinski 
has  suggested  that  the  pancreas  of  persons  in  whom 
accessory  pancreatic  masses  are  met  with,  as  well  as  those 
of  normal  individuals,  develops  from  two  only  of  the 
three  buds  which  are  now  known  to  be  present  in  the 
embryo.  Under  ordinary  circumstances  the  third  out- 
growth remains  as  a  rudiment,  but  occasionally  it  persists, 
and,  undergoing  a  limited  amount  of  development,  be- 
comes attached  to  the  gastric  or  intestinal  wall  as  an 
accessory  pancreas.  Both  these  hypotheses  only  succeed 
in  explaining  those  cases  in  which  two  masses  are  present 
by  supposing  that,  in  rare  instances,  a  third  or  fourth 
pancreatic  bud  is  present  in  the  embryo.  Glinski  sup- 
poses that  in  such  cases  the  dorsal  as  well  as  the  ventral 
outgrowth  is  double.  In  disproof  of  these  explanations 
Opie  quotes  two  cases  observed  by  him.  In  one  there 
was  pancreatic  tissue  in  the  walls  of  the  stomach,  duode- 
num, and  the  lesser  papilla,  and  in  the  other  in  the  duode- 
nal wall  above  the  pancreas  and  in  the  papilla  of  the  duct 


Anatomical  Anomalies  55 

of  Santorini.  He  points  out  that,  should  an  accessory 
pancreas  arise  by  persistence  of  one  of  the  two  ventral 
outgrowths,  it  can  only  be  carried  by  lengthening  of 
,  the  intestine  downwards  towards  the  duodenum,  while, 
should  it  arise  from  part  of  a  double  dorsal  outgrowth, 
it  can  only  be  carried  upwards  towards  the  stomach, 
but  that,  in  these  two  cases,  there  were  two  accessory 
glands  above  the  pancreas,  which  can  only  be  explained 
by  the  occurrence  of  a  triple  primitive  dorsal  rudiment — 
a  condition  which  is  unknown  in  the  development  of  any 
vertebrate  animal. 

The  explanation  which  he  himself  offers  is  similar  to 
that  given  by  Helly  for  the  presence  of  pancreatic  tissue 
in  the  papilla  of  the  duct  of  Santorini.  Helly  believes 
that  lateral  branches  from  the  dorsal  embryonic  outgrowth 
may,  at  an  early  stage  of  development,  penetrate  the 
wall  of  the  intestine,  and  later,  becoming  separated  from 
the  rest,  acquire  new  ducts,  thus  giving  rise  to  the  con- 
dition found  in  some  cases  after  birth.  Opie,  extending 
this  theory,  supposes  that  accessory  masses  of  pancreatic 
tissue  in  all  parts  of  the  gastro-intestinal  tract  arise  by 
entanglement  of  lateral  branches  of  the  primitive  buds 
in  the  developing  walls  of  the  alimentary  canal,  those 
originating  in  the  dorsal  growth  being  carried  upwards  to 
form  the  gastric  and  upper  duodenal  nodules,  and  those 
from  the  ventral  bud  being  carried  downwards  to  consti- 
tute the  accessory  masses  of  gland  substance  met  with 
in  the  lower  duodenum,  jejunum,  and  ileum. 

Other  anatomical  anomalies  of  the  pancreas  have  been 
described,  although  they  are  not  numerous.  Hertz  re- 
cords a  case  in  which  there  was  falling  forwards  of  the 
gland ;  Cacchini  describes  an  instance  in  which  there  was 
congenital  displacement  of  the  head  of  the  gland,  asso- 
ciated with  gastroptosis ;  and  cases  have  been  reported 
in  which  the  tail  of  the  organ,  normally  its  most  movable 
part,  has  been  dragged  into  abnormal  situations  by  a 


56         The  Pancreas:  Its  Surgery  and  Pathology 

wandering  spleen.  Klebs  states  that  the  pancreas  may 
be  pushed  downwards  by  tight  lacing,  and  that  retro- 
peritoneal tumours  and  aneurysms  of  the  adjacent 
vessels  may  carry  it  upward. 

Although  the  pancreas  is  one  of  the  most  firmly  fixed 
organs  in  the  abdominal  cavity  it  has  been  occasionally 
met  with  in  hernial  sacs,  and  Dobrzycki  describes  a  case 
in  which  a  movable  pancreas,  giving  rise  to  symptoms 
resembling  those  of  movable  kidney,  was  present  in  a 
man  as  the  result  of  a  fall  from  a  height.  The  pancreas 
formed  part  of  the  contents  of  27  out  of  276  cases  of 
diaphragmatic  hernia  collected  by  Lacher,  and  in  one 
case  described  by  Claessen,  it  had  passed  through  a  rent 
in  the  diaphragm  into  the  thoracic  cavity.  Two  cases  of 
congenital  umbilical  hernia  in  which  the  pancreas  was 
found  in  the  sac  are  recorded,  and  Rose  met  with  a  similar 
relation  of  the  gland  in  an  umbilical  hernia  in  a  woman  of 
sixty-four.  One  case  in  which  the  pancreas  was  appa- 
rently entirely  wanting  has  been  described. 

The  anatomical  variations  of  the  pancreatic  ducts,  and 
also  of  the  common  bile-duct,  have  important  bearings 
upon  the  pathology  of  the  pancreas,  and  particularly  upon 
the  pathology  of  pancreatitis.  It  is  therefore  important 
that  they  should  be  discussed  in  detail. 

The  common  bile-duct  may  be  divided  into  four  por- 
tions : 

1.  The  supraduodenal  part. 

2.  The  retroduodenal  part. 

3.  The  pancreatic  part. 

4.  The  intraparietal  part. 

Starting  by  the  junction  of  the  cystic  and  hepatic  ducts, 
it  courses  along  the  free  border  of  the  lesser  omentum, 
associated  with  the  portal  vein  and  hepatic  artery.  Then 
passes  behind  the  first  part  of  the  duodenum,  and  soon 
comes  into  relation  with  the  pancreas.  Finally  it  pierces 
the  wall  of  the  second  part  of  the  duodenum  along  with 


Anatomical  Anomalies 


57 


the  duet  of  Wirsung.  The  first  two  portions  are  unim- 
portant as  regards  the  pancreas,  but  the  relations  of  the 
remaining  sections  have  considerable  bearing  upon  the 
etiology  of  diseases  of  that  organ. 

The  third,  or  pancreatic,  portion  of  the  common  bile- 
duct  measures  from  20  to  25  mm.  in  length.  It  extends 
from  the  inferior  border 
of  the  first  part  of  the 
duodenum  to  the  point 
where  the  duct  penetrates 
the  wall  of  the  second 
part.  This  portion  of  the 
common  duct  crosses  a 
small  quadrilateral  area, 
bounded  above  by  the  in- 
ferior border  of  the  first 
part  of  the  duodenum, 
below  by  the  superior 
border  of  the  third  part, 
externally  by  the  inner 
border  of  the  second  part, 
and  internally  by  the  su- 
perior mesenteric  vein. 
Anteriorly  it  is  closely 
applied  to  the  posterior 
surface  of  the  head  of  the 
pancreas.  iVccording  to 
Helly,  this  portion  of  the 
common  duct  is  com- 
pletely embraced  by  the  head  of  the  gland  in  62  per  cent, 
of  bodies,  and  lies  in  a  deep  groove  in  the  remaining  38 
per  cent.  Bunger,  in  a  careful  examination  of  fifty-eight 
subjects,  found  that  in  2  5  per  cent,  the  duct  ran  in  a  groove 
and  in  75  per  cent,  was  entirely  enclosed  in  pancreatic 
tissue.  Wyss  investigated  the  relation  of  the  common 
duct  to  the  pancreas  in  twenty-two  bodies,  and  found 


Fig .  2  6 . — Diagram  showing  rela- 
tions of  the  common  bile-duct  to  the 
duodenum  (viewed  from  behind) : 
I,  Supraduodenal  portion  of  the 
common  bile-duct;  2,  retroduo- 
denal  portion  of  the  common  bile- 
duct;  3,  pancreatic  portion  of  the 
common  bile-duct;  4,  intraparietal 
portion  of  the  common  bile-duct 
(after  Testut). 


58         The  Pancreas:  Its  Surgery  and  Pathology 

that  it  was  surrounded  by  the  tissue  of  the  gland  in  seven 
(31.7  per  cent.),  and  grooved  the  posterior  surface  of  the 
head  in  fifteen  (68.1  per  cent.).  These  variations  in  the 
relations  of  the  duct  to  the  pancreas  are  important,  for 
it  is  obvious  that  swelling  of  the  gland,  when  the  duct 
passes  through  the  substance  of  the  head,  may  compress 


Portal  vein 


Hepatic  artery 

Hepatic  duct 


Neck  of  gall- 
bladder and 
cystic  duct 


Hepatic  artery 

Splenic  vein 
Body  of  pancreas 


Superior  mesenteric 
arterv  and  vein 


Infrrior  pancre- 
atic and  duo- 
denal artery 


Common  bile- 
duct 


Uncinate  process 


Fig.  27. — Diagram  showing  the  common  bile-duct  passing  through 
the  head  of  the  pancreas,  a  portion  of  which  has  been  reflected 
(viewed  from  behind)  (after  Testut). 


it  and  lead  to  occlusion,  while  when  it  is  contained  in  a 
groove  it  may  be  pushed  aside  and  escape  compression. 

The  intraparietal,  or  interstitial,  portion  of  the  common 
bile-duct  comprises  that  portion  of  the  canal  which  is 
contained  in  the  thickness  of  the  wall  of  the  duodenum. 
Its  relation  tO  the  duct  of  Wirsung,  and  its  union  with 
the  termination  of  the  chief  excretory  channel  of  the 


Anatomical  Anomalies 


59 


pancreas  to  form  the  diverticulum  of  Vater,  have  already 
been  described. 

The  mode  of  formation  of  the  ampulla  of  Vater,  and  the 
terminations  of  the  common  bile-duct  and  pancreatic 
duct,  are  liable  to  great  variation,  and  these  variations 
will  be  seen  to  be  of  considerable  importance  when  we 
come  to  consider  the  diseases  of  the  pancreas.  Letulle 
and  Nathan  Lorrier  distinguish  four  types : 

1.  The  first,  or  normal,  arrangement,  in  which  the 
ducts  unite  to  form  the  ampulla  of  Vater,  has  already 
been  dealt  with  (Figs.  19  and  28,  a). 

2.  In  the  second  type  the  pancreatic   duct  joins  the 


I^RD. 


Fig.  28. — Diagram  of  the  four  methods  by  which  the  common  bi'e- 
duct  and  duct  of  Wirsung  enter  the  duodenum:  C.  D,  Common  bile- 
duct;  P.  D,  pancreatic  duct;  V,  ampulla  of  Vater;  O,  common  orifice; 
C,  cup-shaped  depression  in  the  wall  of  the  duodenum;   P,  papilla. 

common  duct  some  little  distance  from  the  duodenum; 
the  ampulla  of  Vater  is  absent,  and  the  united  ducts  open 
into  the  duodenum  by  a  small,  flat,  oval  orifice  (Fig.  28,  b). 

3.  In  the  third  type  the  two  ducts  open  into  a  small 
fossa  in  the  wall  of  the  duodenum,  while  the  caruncle 
and  ampulla  of  Vater  are  both  absent  (Fig.  28,  c). 

4.  In  the  fourth  type  the  caruncle  is  well  developed, 
but  the  ampulla  of  Vater  is  absent,  the  two  ducts  opening 
side  by  side  at  the  apex  of  the  caruncle.  In  eleven  out  of 
one  hundred  specimens  examined  by  Opie  the  arrange- 
ment described  in  this  last  type  was  present  (Fig.  28,  d). 

5.  Rarely  the  common  bile-duct  unites  with  the  duct 


6o         The  Pancreas:  Its  Surgery  and  Pathology 

of  Santorini  instead  of  with  the  duct  of  Wirsung,  as  in  a 
specimen  preserved  in  the  Museum  of  the  Royal  College 
of  Surgeons  (Fig.  29). 

The  A^ariations  met  with  in  the  two  pancreatic  ducts 
are  well  shown  in  a  series  of  one  hundred  cases  investi- 
gated with  regard  to  this  point  by  Opie.  In  every  case 
he  found  that  both  ducts  were  present,  although  occa- 
sionally one  or  the  other  was  so  small  that  it  was  demon- 
strated with  difficulty;    the  duct  of  Wirsung  and  the 


Fig.  29. — Photograph  of  a  specimen  in  the  Hunterian  Museum  of 
the  Royal  College  of  Surgeons,  showing  the  common  bile-duct  joining 
the  duct  of  Santorini  (anatomical  series  277  A). 

common  bile-duct  always  entered  the  duodenum  together, 
while  the  duct  of  Santorini  invariably  opened  into  the 
intestine  at  a  higher  level.  In  ninety  specimens  the  two 
pancreatic  ducts  anastomosed  within  the  substance  of 
the  gland;  in  ten  there  were  two  wholly  independent 
ducts.  On  investigating  the  relative  size  and  the  patency 
of  the  ducts,  he  found  that  out  of  the  ninety  cases  in  which 
ducts  anastomosed  the  duct  of  Wirsung  was  the  larger  in 
eighty-four ;  in  these  the  duct  of  Santorini  was  patent  in 
sixty-three,  and  impervious  in  twenty-one.     The  duct  of 


Anatomical  Anomalies 


6i 


Santorini  was  larger  than  the  duct  of  Wirsung  in  six, 
but  the  latter  was  jjatent  in  all.  Of  the  ten  in  which  no 
anastomosis  between  the  ducts  could  be  discovered,  the 


Fig.  30. — Diagram  to  show  the  variations  in  the  ducts  of  Wirsung  and 
Santorini  (after  Opie). 


duct  of  Wirsung  was  the  larger  of  the  two  in  five,  and  the 
duct  of  Santorini  in  the  other  five.  So  that  in  89  per 
cent,  of  the  cases  the  duct  of  Wirsung  was  the  main  excre- 


62         The  Pancreas:  Its  Surgery  and  Pathology 

tory  channel  of  the  pancreas,  and  in  21  per  cent,  the  duct 
of  Santorini  was  apparently  obliterated  near  its  termina- 
tion, and,  even  in  those  instances  where  it  was  patent,  it 
was  found  to  diminish  in  size  as  it  approached  the  duode- 
num. Thus  the  duct  of  Santorini  could  not  be  relied 
upon  to  supplement  the  duct  of  Wirsung  in  at  least  31 
per  cent,  of  the  cases  if  the  latter  was  obstructed.  More- 
over, it  must  be  borne  in  mind  that  the  duct  of  Santorini. 


Large  accessory  duct 


Fig.  31. — Drawing  of  a  preparation  showing  a  large  accessory 
pancreatic  duct  opening  into  the  ampulla  of  Vater  (Royal  College  of 
Surgeons  Museum,  277  B). 


even  if  patent  and  communicating  with  the  duodenum, 
may  itself  be  compressed  by  a  moderate  sized  gall-stone 
passing  down  the  pancreatic  portion  of  the  common  bile- 
duct. 

In  an  earlier  observation  Schirmer  obtained  somewhat 
similar  results.  He  examined  the  pancreas  in  one  hun- 
dred and  four  bodies  and  found  that  in  sixty-six  (6^  per 
cent.)  there  were  two  ducts  opening  into  the  intestine 
and   communicating  with  the   substance   of  the  gland, 


Anatomical  Anomalies.  63 

while  in  thirty-seven  cases  (35  per  cent.)  the  two  ducts 
did  not  anastomose,  or  one  or  other  did  not  open  into  the 
duodenum.  In  one  case  three  ducts  were  present.  A 
specimen  showing  a  similar  anomaly  is  preserved  in  the 
Museum  of  the  Royal  College  of  Surgeons  (Fig.  31).  It 
was  discovered  during  dissection  by  the  prosector  to 
the  college,  W.  U.  Pearson. 

Literature 

Bunger:   Med.  Press,  1902,  p.  523. 

Ecker:  Zeitschr.  f .  rationelle  Medicin,  1862. 

Engel:   Medicin.  Jahrb.,  Wien,  1840. 

Gegenbaur:   Reichert's  Archiv,  1863. 

Generisch:   Verhandl.  internat.  mad.  Congress,  1890. 

Glinski:    Virchow's  Archiv,   1901,  clxiv,   132. 

Helly:  Archiv.  f.  mik.  Anat.,  Hi,  773. 

Hyrtl:   "Topograp.  Anatomic." 

Klob:  Zeitschr.  d.  Gesellsch.  d.  Aertze,  Wien,  1859. 

Lens:    Boston  City  Hosp.  Rep.,  1905,  p.  172. 

Nauwerck:    Zeigler's  Beitrage,  xii,   1893. 

Neumann:    Archiv.  f.  Heilkunde,  xi,  1870. 

Nicholls:    Montreal  Med.  Journ.,  Dec,  1900. 

Opie:   "Diseases  of  the  Pancreas,"  1903. 

RoUeston:    Journ.  Anat.  and  Physiol.,  xxviii,  12. 

Santos:   Medical  Congress,  Lisbon,  1906. 

Schirmer:   "Beitrag  zur  Geschichte  und  iVnatomie  des  Pancreas,"  1893. 

Inaug.  Dissert.,  Basel,  1893. 
Symington:  Journ.  Anat.  and  Physiol.,  xix,  292. 
Turner:   Lancet,  Dec.  3,  1904,  p.  1566. 
Vidal:   Dix-huitieme  Congres  de  Chirurgie,  Paris,  1905. 
Wagner:    Archiv.  f.   Heilkunde,   1862. 
Weichselbaum :    Bericht.  d.  Rudolf stiftung.,  1884. 
Wright:   Journ.  Boston  Soc.  Med.  Sci.,  1901,  v,  497. 
Zenker:   Virchow's  Archiv,  xxi. 


CHAPTER  V 

SURGICAL  ANATOMY 

The  intimate  relations  of  the  head  of  the  pancreas  to 
the  duodenum  may  lead  to  invasion  of  that  part  of  the 


4i»^ 


Fig.  32.- — Invasion  of  the  duodenum  by  carcinoma  of  the  head  of  the 
pancreas  (Leeds  Path.  Museum,  EE  204  A). 

intestine  by  disease  of  the  gland,  and,  conversely,  a  pri- 
mary growth  of  the  duodenum  may  secondarily  involve 

64 


Surgical  Anatomy 


65 


the  pancreas.  Gallaudet  has  described  a  case  in  which  a 
cancer  of  the  head  of  the  pancreas  so  far  obHterated  the 
lumen  of  the  duodenum  as  to  call  for  gastro-enterostomy, 
and  we  have  recently  had  under  our  observation  a  case  in 
which  a  malignant  growth  of  the  duodenum  gradually 
invaded  the  pancreas  and  eventually  gave  rise  to  a  severe 
grade  of  diabetes.  Specimens  showing  invasion  of  the 
duodenum  by  pancreatic  growth  are  preserved  in  the 
Museum  at  St.  George's  Hospital  (201  A)  and  in  the 
Leeds  Pathological  Museum  (EE  204  A,  EE  204  B).  An 
example  of  the  converse  condition  is  to  be  seen  at  St. 


Fig-   33- — Sarcoma  of  the   pancreas  invading  the   duodenum   (Leeds 
Path.  Museum,  EE  204  B). 


Mary's.  The  duodenum  may  also  be  compressed  or  dis- 
torted by  cysts  or  tumours  of  the  pancreas,  or  may  be 
involved  in  a  pancreatic  abscess  which  may  discharge 
itself  into  the  lumen  of  the  gut. 

The  proximity  of  the  pancreas  to  the  stomach  (Fig.  34) 
renders  it  liable  to  invasion  by  ulcer  or  cancer  of  that  organ, 
and  fixation  of  the  stomach  by  adhesions,  whether  they 
arise  from  disease  of  the  pancreas  or  of  the  stomach  itself, 
may  lead  to  a  train  of  symptoms  when  the  latter  organ  is 
distended  with  food,  owing  to  the  limitation  of  its  move- 
ments in  a  downward  direction,  as  well  as  giving  rise  to 
5 


66        The  Pancreas:  Its  Surgery  and  Pathology 


pain,  from  interference  with  its  normal  peristaltic  move- 
ments. Adhesion  to,  or  invasion  of,  the  pancreas  by  a 
cancerous  growth  of  the  stomach  or  pylorus  not  only  adds 
to  the  danger  of  operations  undertaken  for  the  relief  or 
cure  of  the  condition,  but  renders  a  return  of  the  disease 
much  more  probable  if  removal  is  attempted.  Von 
Mikulicz's  experience  on  this  point  is  most  instructive; 
in  ninety-one  partial  gastrectomies,  without  injury  to  the 
pancreas,  twenty-five  died  as  the  result  of  operation,  a 
mortality  of  27.5  per  cent. ;  but  in  thirty  cases  in  which 

the  pancreas  was 
injured  or  partly 
removed  the  mor- 
tality was  70  per 
cent.  {i.  e.,  twenty- 
one  deaths),  most- 
ly from  peritonitis. 
Nevertheless,  as 
part  of  the  oper- 
ation of  gastrec- 
tomy, a  partial 
pancreatectomy 
has  been  success- 
fully performed  by 
one  of  us,  by  Mik- 
ulicz, by  Kocher 
and  others.  Fen  wick  investigated  one  hundred  cases  of 
cancer  of  the  pylorus  and  found  that  the  pancreas  was 
adherent  in  six ;  in  another  series  of  one  hundred  cases  of 
malignant  disease  of  the  cardiac  end  of  the  stomach  the 
pancreas  was  adherent  in  sixteen,  and  in  the  same  num- 
ber of  cases  of  cancer  of  the  lesser  curvature  or  posterior 
wall,  it  was  adherent  in  nineteen. 

Chronic  ulcers  of  the  stomach,  when  they  become  ad- 
herent to  the  pancreas,  may  set  up  pancreatitis,  and  even 
give  rise  to  an  abscess,  as  is  shown  in  the  case  of  a  man 


Fig.  34. — Diagram  showing  the  relations  of 
the  stomach  to  the  pancreas  (after  Testut). 


Surgical  Anatomy 


67 


who  was  operated  upon  by  one  of  us  six  years  ago.  In 
this  instance  the  pancreatic  abscess  had  burst  into  the 
stomach,  giving  rise  to  acute  gastritis,  with  extremely 
foul  stomach  contents  and  incessant  vomiting.  His 
symptoms  were  relieved,  and  he  was  eventually  cured, 
by  drainage  of  the  stomach  into  the  jejunum  through 
a  gastro-enterostomy  opening.  In  another  case,  also  a 
man,  an  ulcer  of  the  posterior  wall  had  become  adherent 


Fig.  35. — Chronic  ulcer  of  the  posterior  wall  of  the  stomach  eroding  the 
pancreas  (Fenwick,  London  Hospital  Museum). 

to  the  pancreas  and  produced  a  cavity  in  the  substance 
of  the  gland  into  which  the  tip  of  the  finger  could  be 
passed.  A  third  case  may  be  cited  in  which  a  middle- 
aged  man  had  suffered  from  symptoms  of  chronic  gas- 
tric ulcer  for  several  years,  with  vomiting  of  coffee-ground 
material.  On  exposing  the  stomach  no  evidence  to  ac- 
count for  the  trouble  could  be  found,  but  when  it  was 
opened  a  large  ulcer,  one  and  a  half  by  three  inches  in 
diameter,  was  discovered  on  the  posterior  wall,  eroding 


68         The  Pancreas:  Its  Surgery  and  Pathology 

the  pancreas.  Posterior  gastro-enterostomy  was  followed 
by  complete  and  permanent  recovery. 

The  relations  of  the  pancreas  to  the  peritoneum  are 
of  the  utmost  importance,  both  from  a  surgical  and  patho- 
logical point  of  view.  The  retroperitoneal  position  of  the 
organ  is  of  great  importance,  for  it  explains  not  only  the 
course  taken  by  pus  in  some  cases  of  suppurative  pancrea- 
titis, upwards  to  the  diaphragm  and  downwards  towards 
the  left  iliac  fossa,  but  also  how  such  collections  may  be 
reached  from  the  right  or  left  loin,  especially  the  latter, 
by  an  incision  in  the  costo-spinal  angle,  or  from  the  left 
iliac  fossa,  or  between  the  ribs,  when  it  has  travelled  up- 
wards and  presents  as  a  subdiaphragmatic  abscess. 

The  fact  that  the  anterior  surface  of  the  pancreas  pro- 
jects into  the  lesser  sac  renders  it  easy  to  explain  how 
this  cavity  is  invaded  in  inflammatory  affections  or  injury 
of  the  gland,  and,  from  its  shape,  it  is  not  difficult  to  see 
how,  when  it  is  filled  with  fluid,  it  is  in  many  instances 
mistaken  for  a  true  pancreatic  cyst.  The  real  nature  of 
this  variety  of  pseudo-cyst  was  demonstrated  many  years 
ago  by  Jordon  Lloyd.  The  sharply  limited  surfaces  of 
the  pancreas,  as  well  as  the  indefinite  site  of  origin  of  true 
cysts  of  the  gland,  cause  considerable  variation  in  the 
relations  of  any  tumour  which  may  develop.  These 
relations  and  the  variations  induced  by  the  origin  of  a 
cyst  above  or  below  the  transverse  mesocolon,  and  to  the 
right  or  left  of  the  mesentery,  as  well  as  the  mistakes  in 
diagnosis  which  are  likely  to  be  caused  thereby,  will  be 
fully  considered  in  a  subsequent  chapter  (Chapter  XVIII). 

The  situation  of  the  pancreas  at  the  back  of  the  abdom- 
inal cavity  makes  the  technique  of  operations  upon  it 
somewhat  difficult,  unless  it  is  approximated  to  the  abdom- 
inal wall  by  disease,  as  in  the  case  of  pancreatic  cysts, 
or  by  some  special  method,  such  as  has  been  described 
for  exposing  the  biliary  passages.^     Various  routes  have 

^  Robson:   "  Dis.  of  the  Gall-bladder  and  Bile-ducts." 


Surgical  Anatomy  69 

to  be  adopted  according  to  the  situation  of  the  diseased 
part  and  the  direction  of  enlargement  of  the  organ. 

The  operative  methods  by  which  the  gland  can  be 
exposed  may  be  divided  into  transperitoneal  and  retro- 
peritoneal. In  the  transperitoneal  methods  it  is  reached 
by  a  median  or  lateral  incision  in  the  anterior  abdominal 
wall,  and  then  either  through  the  gastro-hepatic  or 
through  the  great  omentum,  or  after  pushing  up  the 
omentum  and  transverse  colon,  through  the  mesocolon. 
In  each  case  the  omental  bursa  is  opened.  Another 
transperitoneal  route,  employed  by  Korte,  and  by  one 
of  us  in  pancreatic  lithotomy  and  when  removing  a  por- 
tion of  the  gland  for  microscopical  examination  in  sus- 
pected cancer, — by  which,  however,  only  the  head  of  the 
organ  can  be  reached, — is  to  force  a  way  along  the  side 
of  the  duodenum,  the  peritoneal  covering  of  which  must 
first  be  incised.  A  third  method,  which  is  also  useful 
in  exposing  the  pancreatic  portion  of  the  common  bile- 
duct,  is  to  incise  the  parietal  peritoneum,  lateral  to  the 
descending  portion  of  the  duodenum,  to  detach  the  duode- 
num from  the  abdominal  wall  and  then  lift  it  inwards, 
separating  it  from  the  front  of  the  kidney,  thus  exposing 
the  posterior  surface  of  the  head  of  the  gland.  The  retro- 
peritoneal methods,  by  incisions  in  the  lumbar  regions, 
only  allow  of  the  head  or  tail  of  the  organ  being  dealt  with, 
and  should  therefore  be  employed  only  when,  through 
the  effects  of  disease,  the  affected  part  is  enlarged  and 
pushed  to  one  side  or  the  other,  as  by  abscess,  cyst,  or 
tumours. 

The  anatomical  relations  of  the  pancreas  to  many 
structures,  including  the  aorta  and  vena  cava,  the  coeliac 
plexus,  the  spleen,  the  left  suprarenal  capsule,  the  left 
kidney,  the  portal  vein,  the  duodenum,  the  stomach  and 
colon,  and  even  the  uterus  during  pregnancy,  as  well  as 
the  common  bile-duct  and  the  middle  colic  artery,  injury 
of  which  is  followed  by  gangrene  of  the  transverse  colon 


7o        The  Pancreas:  Its  S.urgery  and  Pathology 

(Kronlein),  have  all  to  be  remembered  in  undertaking 
operations  upon  the  pancreas. 

Its  relations  to  these  important  structures,  its  fixation, 
and  its  great  vascularity  would  render  an  operation  for 
the  complete  extirpation  of  the  pancreas  extremely  diffi- 
cult, even  if  it  were  justifiable  on  physiological  grounds, 
but  where  disease  is  invading  the  distal  part  of  the  body, 
or  tail,  the  removal  of  that  portion  is  both  justifiable  and 
safe  in  the  case  of  cystic  or  solid,  benign  or  malignant, 
growths. 

The  variations  in  size  of  the  ampulla  of  Vater  have  been 
already  referred  to,  and  the  bearing  of  these  upon  acute 
pancreatitis  will  be  dealt  with  when  that  subject  is  con- 
sidered subsequently. 


CHAPTER  VI 
HISTOLOGY 

The  structure  of  the  pancreas  at  once  recalls  that  of 
the  salivary  glands,  hence  the  names  "abdominal  salivary 
gland,"  "gland  salivaire  abdominale,"  "bauchspeichel- 
druse, ' '  that  have  been  applied  to  it.  The  resemblance  is, 
however,  only  a  superficial  one,  for  although  in  its  broad 
lines  the  pancreas  is  constructed  on  the  same  plan  as  a 
serous  salivary  gland,  such  as  the  parotid,  its  minute 
anatomy  is  much  more  complex,  as  was  first  clearly 
demonstrated  by  the  researches  of  Langerhans  in  1869. 

Like  the  parotid,  the  pancreas  is  a  compound  tubular 
gland,  composed  of  branching  ducts  terminating  in  acini 
of  a  tubular  form.  The  acini  about  the  terminal  ducts  are 
grouped  together  to  form  primary  lobules,  which  in  man 
are  usually  more  or  less  fused  together  to  form  larger 
secondary  lobules  about  the  medium  sized  ducts.  These 
are  again  grouped  together  to  form  tertiary  lobules,  which 
represent  the  smallest  subdivisions  of  the  organ  seen  on 
the  surface  with  the  naked  eye.  The  larger  lobes  of  the 
gland  are  formed  in  a  similar  manner  by  the  union  of  the 
lobules  around  the  larger  ducts.  The  lobules  are  less 
definitely  polygonal  than  in  the  salivary  glands,  and 
they  are  also  less  compactly  arranged,  so  that  the  gland 
is  of  a  looser  and  softer  texture.  The  alveoli  are  much 
larger  and  more  tubular  than  in  the  parotid,  and,  since 
they  are  also  relatively  more  numerous,  fewer  ducts  are 
seen  in  a  given  sectional  area. 

The  arrangement  of  the  connective-tissue  framework 
of  the  normal  pancreas  is  of  importance  in  view  of  the 
changes  that  occur  in  it  as  the  result  of  chronic  inflam- 

71 


72         The  Pancreas:  Its  Surgery  and  Pathology 

matory  affections.  Our  present  knowledge  concerning 
its  arrangement  and  distribution  is  chiefly  due  to  the 
researches  of  J.  Marshall  Flint,  who  has  made  a  number 
of  valuable  observations  on  this  subject,  chiefly  by  means 
of  the  Spalteholz  digestion  process  and  with  Mallory's 
stain.  The  surface  of  the  gland,  as  we  have  seen,  has  no 
true  capsule,  but  is  covered  by  a  loose  thin  coat  of  connec- 
tive tissue.  Within  the  substance  of  the  organ  the  con- 
nective tissue  is  arranged  in  an  interlobular  framework 


Fig.  36. — Piece  digestion  of  a  human  pancreas,  showing  the  Hmiting 
membrane  of  a  lobule  and  the  reticulated  basement  membranes  of  the 
alveoli.  In  the  center  is  an  island  of  Langerhans  with  its  capsule  of 
trabecula;  (X   26)  (Flint). 

of  relatively  large  strands,  which  separate  the  lobes  and 
lobules,  and  an  intralobular  network  of  finer  fibrils,  which 
lie  between  the  individual  acini  and  so  form  a  plexus 
within  the  areas  bounded  by  the  coarser  interlobular 
bundles.  According  to  Flint,  the  interlobular  connective 
tissue  is  much  more  delicate  and  less  abundant  than  in 
the  salivary  glands,  and  is  not  fasciculated,  except  in  the 
neighbourhood  of  the  duct  of  Wirsung,  nor  are  the  connec- 
tive-tissue bundles  so  regularly  arranged.     The  amount 


Histology  73 

varies  in  different  parts ;  in  some  places  only  a  few  strands 
are  found  spanning  the  fissures,  while  in  others  relatively 
thick  processes  bind  adjacent  lobules  together. 

The  secondary  lobules  or  lobule  groups  are  usually 
separated  by  relatively  wide  bands  of  loose  connective 
tissue,  but  the  primary  lobules,  as  pointed  out  above, 
are,  as  a  rule,  not  clearly  defined.  The  intralobular 
framework  is  of  approximately  the  same  form  and  size 
as  in  the  salivary  glands,  although  it  is  somewhat  more 
delicate,  but  its  arrangement  is  quite  different.  It  con- 
sists of  a  fine  network  of  delicate  interlacing  fibres  stretch- 
ing across  the  lobules  between  the  limiting  membranes, 
and  forming  a  reticulated  basement  membrane  which 
supports  the  alveolar  cells.  The  constituent  fibres  pursue 
an  irregular  course  and  are  unequally  distributed,  being 
collected  in  some  parts  into  small  bundles,  while  in  others 
they  are  seen  as  narrow  strands.  Near  the  islands  of 
Langerhans  the  processes  between  the  alveoli  become 
thicker  and  stouter,  forming  septa  which  run  into  the 
capsule  of  the  island.  There  is  a  slight  amount  of  elastic 
tissue  mixed  with  the  fibrous  framework,  but  it  is  almost 
exclusively  confined  to  the  interlobular  regions,  excepting 
around  the  ducts,  which,  even  in  the  intralobular  septa, 
are  surrounded  by  a  delicate  network  of  elastic  fibres. 
As  the  ducts  unite  and  become  larger  the  elastic  tissue 
becomes  heavier  and  thicker,  but  is  never  laminated  as  in 
the  submaxillary  gland. 

The  connective  tissue  lying  between  the  lobes  and 
lobules  contains  a  fair  amount  of  fat.  Connective-tissue 
cells,  and  occasionally  mastzellen,  are  seen  in  the  inter- 
lobular framework,  and  numerous  cells  with  elongated 
or  polygonal  nuclei  lie  in  the  interalveolar  connective 
tissue,  as  a  rule  on  the  side  away  from  the  lumen  of  the 
alveolus. 

The  lobules  do  not  posses  a  definite  hilus,  like  those  of 
the  submaxillary  gland,  but  receive  their  blood-vessels 


74         The  Pancreas:  Its  Surgery  and  Pathology 


and  ducts  by  separate  portals.  These  structures  run, 
together  with  the  nerves,  in  the  intralobular  framework 
as  far  as  the  spaces  separating  the  secondary  lobules, 
but  within  the  secondary  lobules  themselves  the  ves- 
sels course  independently  of  the  ducts  and  enter  the 
primary  lobules  at  a  different  point. 

Both  the  blood-vessels 
and  ducts  are  much  finer 
structures  than  in  the  sali- 
vary glands.  In  radio- 
graphs of  the  pancreas 
taken  after  the  ducts  have 
been  injected  with  mercury 
their  extremely  fine  and 
delicate  character  is  well 
demonstrated.  By  the 
cruder  methods  the  ducts 
can  probably  be  injected 
only  as  far  as  their  lobular 
sections,  but  by  forcing  in 
coloured  injections  under 
pressure  fine  intercellular 
passages  between  the  se- 
creting cells  (Saviotti's  ca- 
nals) can  be  made  out.  It 
has  been  contended  that 
these  fine  ramifications  are 
artifacts  produced  by  the 
pressure,  but  the  fact  that 
Golgi's  silver  chromate 
method  shows  similar  fine  processes  between  the  cells,  and 
even  extending  into  the  cell  substance  (Schaffer),  lends 
support  to  the  results  obtained  by  injection  methods. 

The  walls  of  the  larger  ducts  consist  of  an  inner  thick, 
and  an  outer  loose,  coat  of  connective  and  elastic  tissue. 
The  epithelial  lining  is  formed  by  a  single  layer  of  colum- 


Fig.  37. — Skiagram  of  a  pan- 
creas after  injecting  the  ducts 
with  mercury  (Royal  Coll.  of  Surg. 
Museum). 


Histology 


75 


nar  cells,  which  show  only  faint  longitudinal  striation.  As 
the  ducts  diminish  in  size  the  connective-tissue  coats 
become  less  marked  and  the  epithelium  assumes  a  more 
cubical  character,  until  in  the  intermediate  or  intercalary 
portions  it  is  seen  as  a  single  layer  of  flattened  epithelium, 
the  constituent  cells  of  which  appear  spindle-shaped  in 


'i>^\  .^) 
"^-^' 


Fig.  38. — Origin  of  the  ducts  of  the  pancreas,  as  shown  by  the 
chromate  of  silver  method  (E.  Miiller):  A,  Duct  cut  longitudinally, 
lined  by  columnar  epithelium  giving  off  laterally  the  intercalary  or 
lobular  ductules,  m,  to  the  alveoli,  e.  The  manner  in  which  these 
commence  within  the  alveoli  is  shown  under  a  higher  power  in  B. 


section  and  do  not  stain  w^ell  with  either  acid  or  basic 
dyes.  In  the  largest  trunks  small  mucus-glands  can  be 
seen  in  the  walls.- 

The  minute  structure  of  the  organ  is  best  studied  in 
the  lower  animals,  for  preparations  made  from  the  human 
gland  are  rarely  satisfactory,  owing  to  the  rapid  changes 
that  take  place  after  death  and  the  interval  which  usually 


76         The  Pancreas:  Its  Surgery  and  Pathology 

elapses  before  the  material  can  be  fixed  in  a  hardening 
solution.  It  is  also  possible  to  investigate  the  condition 
of  the  gland  in  animals  under  various  experimental  con- 
ditions, which,  while  reproducing  more  or  less  closely 
those  obtaining  in  the  human  subject  in  a  variety  of 
physiological  and  pathological  states,  cannot  be  secured 
at  will  in  man  himself.  Although  it  is  not  strictly  jus- 
tifiable to  argue  from  the  condition  of  an  organ  under  any 


tory  cells     '^^^  ^J       @  V        %', 

Connective i^^^.^!^'^gs;i=:^^/\(^Mv  ,s^~ 

tissue       '     T7/^^'^^S^^  f,^S^f^&m\        7  ^ 


Inner  gran" 

ular  zone 
of  secre- 
tory cells 


Fig.  39. — From  section  through  human  pancreas;     X450  (subHmate) 
(Bohm  and  Davidoff). 

particular  set  of  circumstances  in  one  animal  to  what 
may  be  expected  in  its  homologue  in  another  under 
similar  conditions,  and  there  are  undoubtedly  some 
differences  to  be  observed  in  the  histology  of  the  pancreas 
in  different  animals,  there  is  a  sufficiently  close  resem- 
blance in  all  the  higher  members  of  the  series  to  make 
the  advantages  of  the  method  outweigh  its  possible 
defects. 

The  alveoli  of  the  pancreas  are  tubular  or  flask-shaped, 


Histology 


77 


and  are  lined  by  a  single  layer  of  columnar  cells  which 
taper  somewhat  towards  their  central  extremities,  where 
they  abut  upon  the  small  irregular  lumen  of  the  acinus. 

The  nuclei  of  the  cells  are  centrally  placed,  as  in  the 
serous  salivary  glands,  and  there  is  also  generally  a  spheri- 
cal para-nucleus.  The  latter  consists  of  a  portion  of  the 
protoplasm  which  stains  more  deeply  than  the  rest,  and 
is  said  to  be  formed  by  extrusion  of  material  from  the 
nucleus  (Gaule,  Nocolaider).  The  protoplasm  of  the 
cells  contains  numerous  granules,  which  stain  deeply 
with  acid  dyes,  such  as  eosin.  The  quantity  and  distri- 
bution of  these  has  been  found  to  depend  upon  the  state  of 
the  gland  as  regards  its 
condition  of  "rest"  and 
"activity." 

In  the  "resting," 
"charged,"  or  "loaded" 
gland  they  occupy  the 
inner  or  central  two-thirds 
of  the  cells,  while  in  the 
' '  active  "  or  "  discharged ' ' 
gland  they  are  compara- 
tively scanty,  and  are 
limited   to  the   inner  half. 

According  to  Heidenhain,  during  the  first  stage  of  diges- 
tion (six  to  ten  hours)  the  granules  gradually  disappear 
and  the  granular  inner  zone  diminishes  in  size ;  in  the  sec- 
ond stage  (ten  to  twenty  hours)  the  inner  zone  is  granular 
and  greatly  increased  in  size,  while  the  outer  is  small,  and 
during  hunger  the  outer  zone  again  enlarges.  All  the 
cells  are  not,  however,  in  the  same  stage  at  the  same 
time,  and  while  in  some  the  granular  zone  is  narrow,  in 
others  it  may  be  comparatively  broad.  The  changes 
observed  in  the  granules  during  digestion  point  to  their 
being  the  zymogen,  or  precursor  of  the  digestive  ferment 
secreted  by  the   pancreas.     Kuhne   and   Sheridan   Lea, 


Fig.  40.— Alveoli  of  rabbit's 
pancreas  during  rest  (a)  and  dur- 
ing activity  (b)  (Kuhne  and  Lea). 


78        The  Pancreas:  Its  Surgery  and  Pathology 

watching  the  effect  produced  in  the  Hning  gland  of  the 
rabbit  by  the  injection  of  pilocarpin,  found  that  secretion 
of  pancreatic  juice  is  accompanied  by  a  diminution  in 
the  size  of  the  cells  and  a  discharge  of  the  granules  of  the 
inner  zone.  According  to  Macallum  and  Steinhaus,  the 
nuclei  possess  safranophilous  nucleoli,  and  as  the  nucleus 
loses  its  safranophilous  substance  the  cell  substance  ac- 
quires safranophilous  granules.  These  authors  conclude 
that  the  chromatin  of  the  nucleus  gives  rise  to  a  substance, 
pro-zymogen;  sometimes  it  is  dissolved  in  the  nuclear 
substance,  sometimes  collected  in  masses  (plasmosomes) ; 
finally  it  diffuses  out  into  the  cell  protoplasm,  and  there 
meets  with  a  constituent  of  the  latter  to  form  zymogen 
proper. 

The  protoplasm  between  the  granules  only  stains  faintly 
with  nuclear  or  basic  dyes,  but  the  outer  clear  zone  stains 
well.  The  latter  is  of  a  homogeneous  character,  although 
in  some  instances  it  is  seen  to  be  faintly  striated. 

Lying  in  the  lumen  of  the  acini,  and  sending  processes 
between  the  secreting  epithelium,  are  small  spindle- 
shaped  or  branched  cells,  which,  from  their  position  and 
relation,  are  known  as  "centro-acinar  cells."  They  act 
as  supporting  elements  for  the  walls  of  the  acini,  and, 
according  to  Langerhans,  are  a  continuation  of  the  cells 
of  the  smaller  duct  radicles,  to  which  they  bear  a  strik- 
ing resemblance. 

Langerhans,  in  his  description  of  the  pancreas  in  1869, 
first  drew  attention  to  those  characteristic  structures 
now  known  as  "intertubular  cell-clumps,"  "interacinar 
islands,"  or  "the  islands,  or  areas,  of  Langerhans."  These 
are  ovoid  groups  of  small  spherical  or  polygonal  cells, 
which,  in  man,  are  apparently  irregularly  scattered  through 
the  gland  substance,  but  in  some  animals,  such  as  the 
cat,  occupy  a  definite  position  in  the  centre  of  the  lobules 
(Opie).  In  adult  life  no  connection  between  the  islands 
and  the  duct  system  of  the  gland  can  be  made  out,  but 


Histology 


79 


they  are  found  to  be  intimately  related  to  the  blood- 
vessels. 

The  structure  and  relations  of  the  interacinar  islands 
have  been  the  subject  of  numerous  researches  on  the  part 
of  a  large  number  of  investigators,  who,  while  agreeing 
on  some  points,  differ  in  their  descriptions  in  many  impor- 
tant particulars.  All  those  who  have  devoted  attention 
to  the  subject  agree  that  very  similar  structures  are 
found  in  all  vertebrates,  but,  while  some  regard  them  as 
permanent  bodies  prob- 
ably endowed  with  spe- 
cial functions,  others 
look  upon  them  as  be- 
ing of  a  temporary  na- 
ture and  consider  that 
they  are  in  reality  rest- 
ing acini. 

Harris  and  Gow  in 
1894  described  three 
main  types  in  different 
animals : 

1 .  Those  in  which  the 
islands  were  not  unlike 
lymphoid  tissue,  con- 
sisting of  many  deeply 
stained  nuclei  with  lit- 
tle or  no  distinct  cell  protoplasm  (e.  g.,  the  guinea-pig). 

2.  Masses  of  non-granular  cells  with  distinct  out- 
lines, which  were  joined  in  an  irregular  network  {e.  g., 
armadillo) . 

3.  Compound  cell-groups  in  which  the  islands  were 
divided  by  strands  of  connective  tissue  into  smaller  groups 
(e.  <^.,  human). 

in  1899,  however.  Von  Ebner  stated  that  all  these 
types  could  be  found  in  one  and  the  same  animal,  and 
suggested  that  the  different  appearances  depended  upon 


Fig.  41. — Microphotograph  of  nor- 
mal human  pancreas  showing  an  island 
of  Langerhans  and  its  relation  to  the 
blood-vessels  ( X  50). 


8o        The  Pancreas:  Its  Surgery  and  Pathology 

the  amount  of  blood  in  the  capillaries.  Subsequent 
investigation  has  shown  that  the  cells  are  of  a  similar 
type  in  all  mammals  and  that  the  classification  adopted 
by  Harris  and  Gow  does  not  hold  good. 

The  cells  are  always  smaller  than  the  gland  cells,  and 
each  possesses  a  centrally  placed  round  or  oval  nucleus. 
The  nuclei  differ  from  those  in  the  secreting  cells  by  being 
usually  larger,  relative  to  the  amount  of  cell  protoplasm, 
and  having  a  very  fine  chromatin  network  with  small 
nucleoli.  The  protoplasm  of  the  well-defined  cell  bodies 
is  very  finely  granular,  containing  numerous  very  small 
fat  droplets.  It  does  not  stain  at  all  with  basic  nuclear 
dyes,  such  as  haematoxylin,  but  has  some  affinity  for  eosin 
and  other  acid  stains.  The  appearance  of  the  cells  differs 
somewhat  in  some  members  of  the  vertebrate  series ; 
thus,  in  birds  the  cells  are  generally  small,  oblong  in  shape, 
and  stain  very  poorly ;  in  the  frog  the  preponderant  cells 
are  tall  and  columnar,  and  are  arranged  in  single  rows 
between  the  blood-vessels,  so  that  each  cell  is  in  contact 
with  blood  capillaries  on  two  sides.  This  arrangement 
of  the  cells  in  rows  between  the  blood-vessels,  so  charac- 
teristically seen  in  the  amphibia,  is  found  in  the  mammalia 
to  some  extent,  although  in  them  several  rows  of  cells 
usually  intervene  between  two  adjacent  capillaries. 

All  observers  are  agreed  that  the  islands  of  Langerhans 
are  richly  vascularised,  but  there  is  some  divergence  of 
opinion  as  to  the  nature  of  the  vessels.  The  most  recent 
observations  are  those  of  Pensa  (1905)  and  Lydia  M.  De 
Witt  (1906) .  Pensa  states  that,  as  the  result  of  injections 
of  the  blood-vessels  in  a  large  number  of  different  animals, 
he  was  able  to  show  that  the  islands  are  mostly  supplied 
by  a  rich  capillary  network  which  is  continuous  with 
the  intertubular  capillary  plexus.  In  some  animals, 
such  as  birds,  guinea-pigs,  and  dogs,  the  larger  islets  may 
have,  in  addition,  a  small  afferent  artery  breaking  up 
into  a  capillary  plexus  and  then  collecting  again  into  a 


Histology  8 1 

single  efferent  vein.  As  Lydia  De  Witt  points  out, 
however,  he  does  not  explain  how  he  distinguishes  the 
arteries  from  the  veins,  and  while  he  states  that  the  con- 
nection is,  as  a  rule,  purely  capillary,  one  of  his  figures 
seems  to  indicate  that  the  connection  with  larger  vessels 
is  common. 

By  reconstructing  the  islands  by  the  Born  wax-plate 
method,  and  by  a  study  of  serial  sections  from  injected 
and  uninjected  preparations,  Lydia  De  Witt  has  made 
most  valuable  contributions  to  our  knowledge  of  their 
morphology  and  histology.     She  comes  to  the  conclusion 
that  in  all  the  animals  she  has  investigated,  including 
man  at  different  ages,  cats,  rabbits,  rats,  birds,  guinea- 
pigs,  and  frogs,  the  cords  of  cells  forming  the  areas  are 
separated  by  large  irregular  anastomosing  vessels,  having 
a  complete  endothelial  wall,  but  little  or  no  adventitia, 
thus  corresponding  to  Minot's  definition  of  "sinusoids." 
The  endothelium  of  the  sinusoids  is  directly  applied  to 
the   epithelium   of   the   islands,    intervening   connective 
tissue  when  present,  as  in  the  human  adult  pancreas, 
being  secondary.     The  vascular  network,   according  to 
her  observations,  is  derived  from  the  branching,  winding, 
and  anastomosing  of  several  large  venous  channels  and 
many  capillaries  which  communicate  intimately  with  the 
interacinar  capillaries.     The  largest  sinusoids  are  situated 
at  the  centre  of  the  islands,  where  the  cells  are  smallest. 
The  periphery  of  the  areas  is  much  less  vascular.     Von 
Ebner  also  considers  that  the  large  blood-vessels  of  the 
islands  are  venous,  and  he  points  out  that  they  are  sur- 
rounded on  all  sides  by  cells  like  the  blood  capillaries  of 
the  liver  lobules. 

By  means  of  preparations  made  by  Golgi's  method 

Pensa  showed  that  the  islands  of  Langerhans  are  supplied 

with  a  very  rich  network  of  nerve  fibres,  which  pass  along 

the  blood-vessels  and  between  the  cells.     The  number 

6 


82         The  Pancreas:  Its  Surgery  and  Pathology 


u 


Fig.  42.— A,  Wax  reconstruction  of  areas  of  Langerhans  from  hu- 
man pancreas  (X  about  245);  B,  wax  reconstruction  of  blood-vessels 
with  surrounding  connective  tissue  in  same  area  (X  about  245)  (De 
Witt). 


Histology 


83 


and  arrangement  of  the  fibres  were  found  to  be  quite 
different  from  those  met  with  in  the  acini. 


Fig.  r. 


A  « 


Fig.  2. 

Fig.  43. — I,  Interior  of  the  model  shown  in  A  in  the  preceding  figure;   2, 
interior  of  the  model  shown  in  B  in  the  preceding  figure  (DeWitt). 


The  relation  of  the  cell  islets  to  the  excretory  ducts  of 
the  pancreas  has  been  investigated  by  Von  Ebner,  Kuhne 


84         The  Pancreas:  Its  Surgery  and  Pathology 


f( 


f. 


\ 


^^^^5^4^,/^ 


and  Lea,  Lewaschew,  and  Dogiel.  The  last  named  made 
use  of  Golgi's  method,  while  the  others  forced  injection 
masses  into  the  ducts.  They  all,  excepting  Lewaschew, 
came  to  the  conclusion  that,  in  the  adult,  the  cell  islets 
are  not  connected  by  permeable  ducts  with  the  excretory 
system  of  the  gland,  but  Lewaschew  found  that  some  of 

the  injection  mate- 
^"7,^    ,  rial    passed    within 

the  islands.  His 
results,  however, 
are  generally  re- 
garded as  having 
been  due  to  acci- 
dental escape  of 
the  injection  mass. 
Lydia  De  Witt,  in 
her  paper,  states 
that  the  reconstruc- 
tion method  and  her 
study  of  serial  sec- 
tions shows  "that 
the  cords  of  cells 
have  the  external 
form  of  branching 
and  anastomosing 
tubules,  with  occa- 
sional alveolus-like 
enlargements ;  they 
are,  however,  solid 
structures  with  no  lumen  and  no  arrangement  of  the  cells 
and  nuclei  which  would  suggest  a  lumen." 

In  speaking  of  the  intralobular  framework  of  the  gland 
it  was  mentioned  that  Flint's  investigations,  by  means 
of  the  Spalteholz  digestion  process,  showed  that  near  the 
islands  of  Langerhans  the  processes  between  the  alveoli 
become  thicker  and  stouter,   forming  septa  which  run 


c 


^^, 


Fig.  44.- — Section  of  an  island  of  Lan- 
gerhans from  the  pancreas  of  a  rat  in 
which  the  veins  were  filled  with  blood, 
showing  the  connection  with  the  large 
vein  and  the  arrangement  of  the  sinusoids 
within  the  island  (X  200)' (De Witt). 


Histology  85 

into  the  capsule  of  the  island.  According  to  Flint, 
this  capsule  is  a  well-defined  structure,  and  the  connective 
tissue  forming  the  framework  of  the  islands  has  a  char- 
acteristic arrangement  in  sharp  contrast  to  that  of  the 
remainder  of  the  lobule.  He  found  that  the  capsule  is 
composed  of  thousands  of  ultimate  fibrils,  which,  on  the 
one  side,  are  connected  with  the  alveolar  network,  and, 
on  the  other,  with  the  septa  or  trabeculae  which  stretch 
across  the  space  within  the  island,  subdividing  it  into 
smaller  lacunse  and  acting  as  a  support  for  the  cells  of 
which  it  is  composed.  Every  island  in  the  gland  has  the 
same  characteristic  appearance  and  general  conformity 
in  the  arrangement  of  its  framework,  and  no  transition 
stages  can  be  found  between  the  two. 

Laguesse,  however,  was  unable  to  find  a  fibrous  tissue 
capsule,  but  describes  a  thin,  homogeneous  layer,  thick- 
ened in  places,  which  forms  a  "pseudo-capsule."  He 
also  states  that  a  thin  amorphous  sheath  accompanies 
the  principal  vessels,  and  may  be  continued  over  the  cap- 
illaries. Von  Ebner  was  also  unable,  as  a  rule,  to  find 
any  connective  tissue,  or  membrana  propria,  between 
the  capillaries  and  cells  of  the  islets. 

These  apparently  contradictory  statements  are  to 
some  extent  explained  by  the  obser\^ations  of  Lydia  De 
Witt.  This  observer  found  that  in  the  frog  no  connective 
tissue  can  be  demonstrated,  either  surrounding  the  areas 
or  around  the  intra-insular  sinusoids,  but  that  in  the 
guinea-pig,  rat,  and  rabbit,  sections  stained  with  Mallory's 
stain  show  a  very  thin  connective-tissue  capsule  separat- 
ing the  island  from  the  surrounding  pancreatic  acini,  and 
delicate  sheaths  of  connective  tissue  covering  the  blood- 
vessels, while  delicate  fibres  also  follow  the  contour  of 
the  cells.  In  the  human  subject  the  age  and  condition 
of  the  body  appear  to  be  most  important  factors  in  deter- 
mining the  amount  and  distribution  of  the  intra-insular 
connective  tissue.     The  pancreas  of  the  new-born  infant. 


86 


The  Pancreas:  Its  Surgery  and  Pathology 


according  to  her,  shows  most  of  the  islands  to  be  situated 
in  the  inter-lobular  connective  tissue,  by  which  they  are 
surrounded,  but  no  connective  tissue  could  be  made  out 
within  the  cell  islets  themselves.  In  a  four-year-old 
child,  although  no  connective  tissue  could  be  demonstrated 
with  ordinary  stains,  Mallory's  stain  revealed  a  delicate 
capsule  and  delicate  sheaths  surrounding  the  blood- 
vessels. Around  most  of  the  cell-islands  of  the  adult  a 
rather  definite  capsule  of  nucleated  connective  tissue 
was  found,  and  in  the  interior  definite  trabeculas,  divid- 


Fig.  45_. — Piece  digestion  of  a  human  pancreas,  showing  the  connec- 
tive tissue  of  an  island  of  Langerhans  from  Fig.  36  (X  135)  (Flint). 


ing  the  islands  into  smaller  compartments  containing  the 
cells,  could  be  seen.  In  some  instances  the  connective 
tissue  formed,  with  the  larger  blood-vessels,  one  or  many 
large  trabeculge  passing  through  the  centre  of  the  area, 
and  from  them  smaller  branches  were  given  off  to  the 
sides,  much  in  the  same  way  as  that  described  and  fig- 
ured by  Flint  (Fig.  45). 

The  very  small  amount  of  connective  tissue  found  in 
the  islands  of  Langerhans  in  animals  and  young  persons, 
and  the  increase  which  apparently  accompanies  advanc- 
ing age  in  man,  as  a  rule,  suggest  that  it  is  probably  a 


Histology  87 

secondary  effect  analogous  to  the  fibrosis  which  is  usually 
associated  with  advancing  years  in  other  organs. 

The  size  and  distribution  of  the  islands  is  not  uniform. 
Laguesse  has  distinguished  five  different  types  in  man, 
varying  from  a  very  small  form,  less  than  100  ji  in  diam- 
eter, to  very  rare,  giant  forms  of  over  400  //  in  diameter. 
He  found,  from  an  average  of  six  bodies,  that  there  is 
rather  less  than  one  island  to  each  square  millimetre  of 
pancreatic  tissue,  and  that  about  0.0 1  per  cent,  of  the 
gland  is  formed  by  the  islands  of  Langerhans. 

Opie  found  that  they  were  more  numerous  in  the  tail, 
or  splenic  end,  than  elsewhere  in  the  human  pancreas. 
He  also  agrees  with  Kasahara  that  the  pancreatic  tissue 
of  the  foetus  and  very  young  children  shows  a  larger  num- 
ber of  islands  than  that  of  the  adult.  He  states  that 
this  can  be  explained  if  it  is  assumed  that  they  are  formed 
during  embryological  development,  and  persist  unchanged 
while  the  secreting  tissue  increases  in  bulk.  Lydia  De 
Witt,  however,  found  that  while  about  0.02  per  cent,  of  the 
pancreas  of  the  adult  consisted  of  insular  tissue,  it  formed 
0.04  per  cent,  of  that  of  the  four-year-old  child  and  only 
0.008  per  cent,  of  the  pancreas  in  the  new-born  infant,  and 
that  the  average  size  of  the  islets  in  the  adult  was  ac- 
tually greater  than  in  either  of  the  other  two. 

The  position  of  the  islands  with  regard  to  the  rest  of 
the  pancreatic  tissue  is  not  constant  in  the  human  sub- 
ject, although  they  are  often  situated  in  the  centre  of  a 
more  or  less  clearly  defined  lobule,  but  in  the  cat  they 
occupy  a  position  near  the  centre  of  the  lobule,  each  of 
which,  in  the  splenic  portion,  contains  an  island  (Opie). 
Their  distribution  in  certain  bony  fishes,  particularly  in 
Lophius  piscatorius  and  Scorpoena  scropha,  is  of  consid- 
erable interest  and  importance,  as  bearing  upon  the 
questions  of  their  origin  and  significance.  Rennie  states 
that  very  large  islets  were  found  in  the  areas  of  pancreatic 
tissue  scattered  along  the  abdominal  vessels  in  all  of  the 


88         The  Pancreas:  Its  Surgery  and  Pathology 

twenty-five  species  he  investigated,  and  that  in  Lophius 
piscatorius  and  Scorpoena  scropha  there  was  constantly 
present  a  very  large,  so-called  "principal  islet,"  indepen- 
dent of  the  pancreatic  tissue,  and  surrounded  by  a  fibrous 
tissue  capsule,  in  the  mesenteric  fold  between  the  portal 
vein  and  mesenteric  artery,  a  short  distance  in  front  of 
the  spleen.  These  principal  islets  are  sufficiently  large 
to  be  distinguished  by  the  naked  eye  and  can  be  dissected 
out  free  from  pancreatic  tissue.  In  the  pancreas  of  the 
guinea-pig  Lydia  De  Witt  met  with  large,  relatively 
isolated  islets  lying  in  the  connective  tissue  around  the 
large  ducts,  especially  about  the  junction  of  the  splenic 
and  middle  thirds,  and,  occasionally,  in  the  mesenteric 
fat  near  the  periphery  of  the  gland,  cell  islets,  which 
appeared  to  be  free  from  the  pancreatic  tissue,  were  met 
with.  The  majority  of  the  islets  were,  however,  closely 
related  to  the  pancreatic  acini.  The  same  observer 
noticed  that  in  all  the  sections  from  the  new-born  infant 
examined  by  her  the  islets  were  situated  in,  and  were 
surrounded  by,  the  interlobular  connective  tissue. 

Light  on  the  vexed  question  of  the  significance  of  these 
remarkable  structures  has  been  sought  by  a  study  of 
their  development,  but  here  again  there  is  considerable 
difference  of  opinion.  Hansemann  believed  that  they 
arose  from  the  interstitial  tissue  and  had  no  connection 
with  the  pancreatic  acini.  Laguesse,  studying  sheep 
embryos,  described  a  double  origin  for  the  islands. 
The  so-called  "primary  islands"  are  said  by  him  to  arise 
from  deeply  staining  units  in  the  single  layer  of  cells 
forming  the  wall  of  the  primitive  pancreatic  tubules. 
By  their  proliferation  these  particular  cells  form  solid 
outgrowths,  which,  later,  becoming  surrounded  by  the 
hollow  outgrowths  which  bud  out  from  the  primitive 
tubules,  constitute  the  primary  cell  islets.  The  secondary 
islands  were  believed  by  Laguesse,  following  Lewaschew, 
to  be  transitory  structures  developed  from  the  acini  and 


Histology  89 

changing  back  into  them  again.  Kiister  states  that  they 
are  derived  from  the  ducts ;  Pearce  beHeves  that  they  are 
developed  from  the  pancreatic  tubules,  and  are  at  first 
solid  and  later  become  vascularised,  a  reticulum  develop- 
ing still  later.  Renaut  states  that  the  primitive  dorsal 
and  ventral  duodenal  outgrowths  form  solid  branches 
which  ramify  in  the  mesentery.  These  later  acquire  a 
lumen,  and  from  their  walls  groups  of  bhnd  pouches  arise, 
which  constitute  the  secreting  acini,  each  group  of  pouches 
representing  a  primary  lobule  of  developed  pancreas. 
In  each  group  of  pouches  there  appears  a  cell,  similar 
to  those  described  by  Laguesse,  and  by  the  continued 
growth  and  multiplication  of  this  the  cell  islet  of  the 
lobule  is  formed. 

The  constant  presence  of  these  structures  at  all  ages 
and  in  so  many  different  animals,  their  early  appearance 
in  embryonic  life,  the  manner  in  which  they  retain  their 
vitality  under  varying  conditions,  their  different  staining 
reactions,  and  peculiar  arrangement,  have  suggested  that 
they  are  independent  vascular  glands,  derived  from  the 
same  embryonic  rudiments  as  the  secretory  acini,  but 
endowed  with  some  special  function.  Although  this  is 
the  view  held  by  most  recent  writers  who  have  devoted 
attention  to  the  subject,  there  are  others,  as  we  have 
already  mentioned,  who  regard  them  as  temporarily 
changed  acini  which  may  again  assume  their  former 
appearance  and  characters.  The  principal  arguments 
advanced  in  favour  of  the  latter  hypothesis  by  its  sup- 
porters are:  (i)  that  the  islets  are  closely  related  to  the 
acini,  from  which  they  are  not  separated  by  any  definite 
capsule,  both  structures  have  a  common  blood-supply, 
and  the  islets  open  into  the  pancreatic  ducts ;  (2)  in  the 
same  sections  various  transition  stages  between  typical 
acini  and  typical  islets  can  be  found;  (3)  the  number  of 
islets  increases  during  activity  of  the  gland  and  dimin- 
ishes during  rest;    (4)  by  prolonged  stimulation  of  the 


90        The  Pancreas:  Its  Surgery  and  Pathology 


'^U^ 


y' 


gland,  either  by  overfeeding  or  by  the  administration  of 
pilocarpin,  it  is  possible  to  transform  secreting  acini 
into  islands  of  Langerhans;  (5)  if  the  pancreas  of  a 
guinea-pig  is  ligatured  near  the  splenic  end  in  two  places, 
and  portions  are  examined  at  intervals  from  between, 
behind,  and  in  front  of  the  ligatures,  while  all  traces  of 
gland  substance  disappear  from  the  tissue  between  and 
behind  the  points  of  constriction,  the  cirrhosed  portion 
in  front  shows  as  many,  if  not  more,  islands  of  Langer- 
hans than  secreting 
acini,    so     that,     al- 

''"'*  ^'*  ^I^4p>  though    the     results 

seen  in  the  last 
named  may  tend  to 
support  the  theory 
that  the  islands  are 
independent  and 
more  resistant  struc- 
tures than  the  acini, 
the  same  cannot  be 
said  for  the  remain- 
ing parts  (Mankow- 
ski).  The  points 
raised  under  the  first 
heading  have  .been 
discussed  in  consid- 
ering the  structure  of  the  islands,  and  it  has  been  shown 
that  the  most  recent  observations  do  not  lend  support 
to  these  contentions.  There  is  no  doubt  that  in  some 
of  the  lower  animals,  such  as  the  rabbit,  in  which  the 
capsule  of  the  islands  is  very  thin,  places  can  be  seen  in 
which  the  island  cells  and  the  gland  cells  appear  to  be 
continuous,  and  that  in  the  foetal  pancreas  affected  with 
congenital  syphilis  the  islands  of  Langerhans  may  be 
continuous  with  the  surrounding  secreting  structures 
(Opie).     But  this  can  be  explained,  in  the  one  case  by 


:^'' 


Fig.  46. — Section  through  the  center 
of  an  island  of  Langerhans  from  the  pan- 
creas of  a  rabbit,  showing  a  connection 
with  the  pancreatic  tubules  at  "p" 
(X  200)  (DeWitt). 


Histology  91 

the  more  or  less  rudimentary  condition  of  the  organ,  and 
in  the  other  by  the  retarding  effects  of  the  pathological 
condition  on  development,  for,  as  we  have  shown,  it  is 
probable  that  the  secreting  cells  and  the  islets  originate 
from  a  common  epithelial  anlage.  With  regard  to  the 
second  point,  it  cannot  be  disputed  that  at  times  struc- 
tures suggesting  transitional  forms  are  met  with,  but  by 
the  study  of  serial  sections  it  can  generally  be  made  out 
that  these  are  either  gland  acini  in  which  the  staining 
reactions  are  abnormal  and  the  characteristic  differentia- 
tion into  zones  is  absent,  or  cell  islets  in  which  the  eosino- 
phile  cells  are  more  numerous  than  usual.  Lydia  De  Witt 
states  that  in  her  experience  she  has  seen  none  that  could 
not  be  explained  in  some  other  and  more  rational  way 
than  by  supposing  that  they  were  transition  forms  between 
secreting  acini  and  cell  islets,  and  that  the  so-called 
transition  forms  have  proved  to  be  merely  resting  pan- 
creatic tubules.  The  same  observer  has  examined, 
measured,  and  counted  large  numbers  of  islands  from  a 
considerable  number  of  guinea-pigs  to  determine  the 
changes  brought  about  by  digestion  and  diet.  The 
animals  were  killed  about  fourteen  hours  after  eating 
and  were  kept  upon  (i)  normal  full  diet,  (2)  without  food 
or  drink,  (3)  on  pure  carbohydrate  diet,  (4)  on  pure  meat 
diet.  She  concluded  that  "while  some  qualitative 
changes  were  noted  in  the  islets, — such  as  an  increase  or 
diminution  of  the  eosinophile  cells,  a  granular  change  in 
the  cells,  atrophy  of  the  cells  with  increase  of  the  inter- 
cellular substance, — there  were  none  which  could  be 
regarded  as  constant  for  any  one  experiment  and  con- 
stantly increasing  with  the  duration  of  the  experiment." 
Opie,  Schulze,  Diamare,  and  Jarotzky  have  arrived  at 
similar  conclusions,  while  Hansemann  believes  that  the 
apparent  increase  during  digestion  is  due  to  a  more 
marked  differentiation  arising  from  the  changes  in  the 
acini.     The  statement  that  prolonged  stimulation  of  the 


92         The  Pancreas:  Its  Surgery  and  Pathology 

gland  by  overfeeding,  or  by  the  administration  of  pilo- 
carpin,  causes  transformation  of  secreting  acini  into 
islands  of  Langerhans  is  based  upon  experiments  carried 
out  by  Lewaschew  in  Heidenhain's  laboratory.  They 
have  not,  however,  been  confirmed  by  other  observers. 
Statkewitsch,  who  has  described  alterations  in  the  secret- 
ing acini  in  several  specimens  of  animals  under  various 
conditions,  thinks  that  they  are  merely  the  results  of 
intense  changes  in  the  gland  cells,  and  are  not  stages  in  a 
transition  to  cell  islets.  Jarotzky,  as  the  result  of  his 
experiments,  comes  to  the  conclusion  that  the  islands  of 
Langerhans  are  independent  structures,  and  are  not 
connected  with  the  altered  gland  acini  met  with  as  the 
result  of  altered  dietetic  conditions.  He  attributes  the 
results  obtained  by  Lewaschew  to  imperfect  fixation. 
After  the  administration  of  pilocarpin  Opie  found  that 
no  increase  in  the  number  of  cell  islets  could  be  detected, 
and  that  no  transition  stages  between  glandular  acini 
and  cell  islet  could  be  seen.  He  points  out  that  in  Lew- 
aschew's  experiments  the  normal  variations  in  the  num- 
ber of  islands  in  various  parts  of  the  gland,  and  in  different 
glands,  are  not  sufficiently  taken  into  account. 

The  more  powerful  physiological  stimulus  afforded  by 
injection  of  secretin  has  recently  been  employed  by  Dale 
in  investigating  this  subject.  He  states  that  the  pro- 
longed administration  of  secretin  produces  changes  in  the 
gland  cells  of  such  a  kind  as  to  assimilate  them  in  arrange- 
ment and  properties  to  those  forming  the  epithelium  of 
the  ductules  and  centro-acinar  cells,  thus  bringing  about 
reversion  to  an  embryonic  type.  The  lumina  of  the 
acini  disappear  and  the  cells  are  brought  into  more  inti- 
mate relation  with  the  blood-vessels.  These  altered 
masses  of  cells  are  regarded  by  Dale  as  being  islands 
of  Langerhans,  and  he  states  that  numerous  intermediate 
forms,  retaining  obvious  traces  of  their  former  alveolar 
structure,    can    be    found.     He    therefore    agrees    with 


Histology  93 

Lewaschew  that  the  cell  islets  are  not  independent 
structures,  but,  as  Laguesse  has  suggested,  represent  an 
internally  secreting  stage  in  the  life  of  the  pancreatic 
tissue.  Further  investigation  of  the  subject  by  this 
method  is,  however,  desirable  before  the  true  interpreta- 
tion of  the  results  described  by  Dale  can  be  arrived  at, 
and  it  is  more  particularly  desirable  that  serial  sections 
stained  by  appropriate  methods  should  be  examined,  and 
that  models  prepared  by  the  Born  wax-plate  method 
should  be  compared  with  those  made  from  normal  cell 
islets,  for  the  evidence  at  present  available  cannot  be 
regarded  as  conclusively  demonstrating  a  structural  con- 
nection of  the  secreting  acini  ~  with  the  cell  islets  in  the 
adult  forms  of  the  higher  types  of  animals. 

The  experiments  of  Mankowski,  in  which  the  pancreas 
was  ligatured  in  two  places,  were  undertaken  to  disprove 
observations  made  by  Schulze,  in  which  it  was  found 
that  the  cell  islets  remained  embedded  in  connective 
tissue,  after  the  glandular  acini  had  been  destroyed  as  the 
result  of  the  changes  produced  by  tying  the  ducts.  Man- 
kowski's  conclusions  have  not,  however,  been  supported 
by  the  experiments  subsequently  undertaken  by  Ssobolew, 
Sauerbeck,  Zunz,  and  De  Witt,  w^ho  confirmed  the  obser- 
vations originally  made  by  Schulze  as  to  the  atrophy  of 
the  gland  tissue  and  preservation  of  the  cell  islands  after 
ligature  of  the  excretory  duct  of  the  gland. 

Ssobolew  also  found  that  if  portions  of  the  gland  are 
transplanted,  the  glandular  parenchyma  disappears,  but 
the  islands  of  Langerhans  are  extremely  resistant  and  re- 
main for  long  unchanged. 

An  interesting  case  has  recently  been  carefully  ex- 
amined and  described  by  S,  G.  Scott,  in  which  a  condition, 
similar  to  that  induced  experimentally  in  animals  by 
ligature  of  the  pancreatic  duct,  was  brought  about  by  an 
obstruction  due  to  a  malignant  growth  of  the  head  of  the 
gland.     The  body  of  the  organ  was  markedly  atrophied 


94        The  Pancreas:  Its  Surgery  and  Pathology 

and  the  duct  was  dilated.  Under  the  microscope  an 
extreme  degree  of  fibrosis  was  found,  and  a  number  of 
cell-groups,  which,  in  serial  section,  had  the  appearance 
and  character  of  cell  islets,  were  seen  embedded  in  the 
fibrous  tissue,  but  no  secreting  glandular  tissue  could  be 
distinguished.     There  was  no  evidence  of  diabetes,  and 


*  ^l^ 


Fig.  47. — Obstruction  of  the  pancreatic  duct  by  carcinoma  of  the 
head  of  the  gland,  giving  rise  to  atrophy  and  fibrosis  of  the  body  with 
persistence  of  the  islands  of  Langerhans  (Scott)  (X  ca  30). 


the  urine  gave  no  reaction  for  sugar  during  life,  in  spite 
of  the  almost  complete  disappearance  of  the  secreting 
parenchyma  of  the  gland. 

Some  observers,  basing  their  theory  on  the  microscop- 
ical characters  of  the  cells,  have  regarded  them  as 
lymphoid  structures,  but  their  origin  from  an  embryonic 


Histology  95 

anlage,  the  arrangement  of  the  cells,  and  their  appearance 
in  well-fixed  preparations,  at  once  differentiate  them  and 
suggest  that  such  an  opinion  can  only  have  originated 
from  the  study  of  imperfectly  prepared  specimens. 

That  they  are  not  embryonal  remains,  as  some  have 
supposed,  is  shown  by  the  fact  that  they  exhibit  no  evi- 
dence of  degeneration  in  adult  life,  and  further  that, 
although  they  appear  to  be  more  numerous  in  the  embryo 
and  in  early  life  than  in  the  adult,  the  disproportion  is 
only  relative  and  not  absolute. 

Literature. 

Dale:   Proc.  Roy.  Soc,  Ixxiii,  1904;  and  Phil.  Tr.  Roy.  Soc.  (B),  cxcvii, 

1904. 
De  Witt:   Journ.  of  Exp.  Med.,  1906,  viii,  193. 
•Diamare:    Internat.  Monatschr.  f.  Anat.  u.  Phys.,  1899,  xvi,  155. 
Dogiel:   Arch.  f.  Anat.  u.  Phys.,  1893.,  Anat.  Abt.,  117. 
Ebner:    Kolliker's  "Handbuch  der  Gewebelehre  des  Menschen,"  1899. 
Flint:   Johns  Hopkins  Hosp.  Rep.,  xii,  1904. 
Hansemann:  Zeit.  f.  klin.  Med.,  1894, xxvi,  191.     Verhand.  der  deutsch. 

path.  Gesellsch.,  1902,  iv,  187. 
Harris  and  Gow:  Journal  of  Physiol.,  1894,  xv,  349. 
Jarotzky:   Virchow's  Archiv,  1899,  ^Ivi,  409. 
Kasahara:   Virchow's  Archiv,  1896,  xxliii,  iii. 
Kiihne  and  Lea:    Untersuch  a.  d.  phys.  Instit.  d.  Univ.  Heidelberg, 

1882,  ii,  488. 
Kiister:   Arch.  f.  mik.  Anat.,  1904,  Ixiv,  i. 
Laguesse:   Compt.  Rend,  de  la  Biol.,  1893,  xlv,  819;    Ibid.,  1894,  xlvi, 

667;    Ibid.,  1895,  xlvii,  669;    Ibid.,  1905,  Iviii,  564.     Journ.  de 

I'Anat.,  1894,  xxx,  591;   Ibid.,  1S96,  xxxii. 
Langerhans:   Inaug.  Dissert.,  Berlin,  1869. 
Lewaschew:   Arch.  f.  mik.  Anat.,  1886,  xxvi,  452. 

Macallum:    Quoted  by  Adami,  Brit.  Med.  Journ.,  Dec.  22,  1906,  1763. 
Mallory:   Journ.  of  Exp.  Med.,  1900,  v,  15. 
Mankowski:   Arch.  f.  mik.  Anat.,  1901,  lix,  286. 
Opie:   "Diseases  of  the  Pancreas,  "  1903. 
Pearce:   American  Journ.  of  Anat.,  1903,  ii,  445.     American  Medicine, 

1903,  vi,  1020. 
Pensa:   Internat.  Monatschr.  f.  Anat.  u.  Phys.,  1905,  xxii,  i. 
Rennie:    Quarterly  Journ.  of  Micros.  Science,  1904,  xlviii,  379.     Zeit. 

f.  Phys.,  1905,  xviii,  23. 
Sauerbeck:  Virchow's  Archiv,  1904,  clxxvii,  Suppl.  Heft.  i.     Verhandl. 

der  deutschen  path.  Gesellsch.  Erganzungsheft.     Centl.  f.  path. 

Anat.,  1904,  XV,  217. 
Schaffer:   Quain's  "Elements  of  Anatomy,"  iii,  iv. 
Schulze:   Arch.  f.  mik.  Anat.,  1900,  Ivi,  491. 
Scott:   Journal  of  Pathology  and  Bacteriology,  January,  1907. 
Ssobolew:    Virchow's  Archiv,  1902,  clxviii,  91. 
Statkewitsch :   Arch.  f.  exp.  Path.  u.  Pharm.,  1894,  xxxiii,  415. 
Steinhaus:   Quoted  by  Adami,  Brit.  Med.  Journ.,  Dec.  22,  1906,  1763. 
Zunz:   Zent.  f.  allg.  Path.  u.  path.  Anat.,  1905,  xvi,  5. 


CHAPTER  VII 

PHYSIOLOGY 

The  anatomical  similarity  of  the  pancreas  to  the 
salivary  glands  led  the  early  observers  to  consider  that 
their  functions  were  also  of  the  same  nature,  and  it  was 
not  until  Bernard  pointed  out,  in  1849,  that  the  pancreatic 
juice  was  concerned  in  the  digestion  of  fats,  and,  in  1856, 
that  it  was  also  capable  of  acting  upon  proteid  material, 
that  the  vastly  greater  importance  of  the  pancreas  as  a 
digestive  organ  came  to  be  recognized.  The  subsequent 
investigations  of  other  workers  upon  the  processes  of 
digestion  have  shown  that  the  pancreas  is  the  digestive 
organ  of  the  body  par  excellence,  it  is  capable  of  dealing 
with  all  the  chief  forms  of  food  material,  its  action  is 
more  energetic  and  complete  than  any  other,  and,  more- 
over, it  prepares  for  absorption  substances,  such  as  fat, 
which  are  little,  if  at  all,  changed  by  the  secretions  of  the 
other  digestive  organs.  The  researches  of  Pawlow  and  his 
colleagues  on  the  work  of  the  digestive  glands  demon- 
strated in  a  masterly  manner  that  the  processes  of  diges- 
tion are  not  made  up  of  a  series  of  isolated  phenomena, 
but  that  each  step  follows  in  an  orderly  manner  as  the 
result  of  the  one  which  precedes  it,  and  that  to  this  rule  the 
pancreas  furnishes  no  exception.  A  study  of  the  mechan- 
ism of  the  pancreatic  secretion  by  Bayliss  and  Starling  has 
resulted  in  the  enunciation  of  a  new  principle  concerning 
the  co-ordination  of  its  digestive  functions  with  those  of 
other  parts  of  the  alimentary  tract,  which  has  opened  up 
a  fresh  field  for  research,  and  promises  to  throw  light 
upon  a  number  of  hitherto  obscure  problems  in  other  re- 
gions of  the  body. 

96 


Physiology  97 

Although  the  digestive  functions  of  the  pancreas  are 
undoubtedly  of  great  importance  in  the  due  maintenance 
of  the  health  of  the  organism,  there  is  reason  to  believe 
that  it  exerts  a  still  more  important  influence  upon  the 
internal  metabolism,  particularly  through  the  control  it 
exerts  upon  the  assimilation  of  carbohydrate  material  by 
the  tissues.  The  salivary  glands,  stomach,  and  intesti- 
nal bacteria  may  to  a  certain  extent  replace  or  supple- 
ment its  digestive  work,  but,  so  far  as  we  know  at  present, 
no  other  organ  can  take  on  its  functions  in  carbohydrate 
metabolism. 

Analyses  of  the  pancreas  by  Oidtmann  show  that  it 
consists  of  74.53  per  cent,  of  water,  24.57  P^r  cent,  of 
organic  matter,  and  0.95  per  cent,  of  inorganic  substances. 
The  same  observer  found  in  the  salivary  glands  of  the 
dog  79  per  cent,  of  water,  20  per  cent,  of  organic  and  i 
per  cent,  of  inorganic  matter.  The  organic  matter  of 
the  pancreas  consists  of  proteids  (albumin,  glob-ulin,  and 
nucleo-proteid) ,  zymogens,  nuclein,  leucin,  xanthin  (1.8 
p.  m.),  hypoxanthin  (3  to  4  p.  m.),  guanin  (2  to  7.5  p.  m.), 
adenin,  inosit,  lactic  acid,  volatile  fatty  acids,  and  fat. 
The  principal  constituent  of  the  cells,  however,  appears  to 
be  a  complex  nucleo-proteid,  which  Hammarsten  regards 
as  identical  with  trypsin.  This  when  boiled  gives  a 
coagulated  proteid  and  a  phospho-gluco-proteid,  and  the 
latter  on  treatment  with  dilute  acid  yields  a  reducing 
substance  having  the  characters  of  a  pentose.  Although 
small  quantities  of  a  pentose  (1-xylose)  can  be  obtained 
from  most  organs  in  the  body,  the  pancreas  yields  over 
four  times  the  proportion  that  can  be  obtained  from  any 
other  structure.  Neuberg  found  2.48  per  cent,  of  the 
dry  weight  of  the  pancreas  was  xylose,  while  from  the 
liver  and  from  the  thymus  only  0.56  per  cent,  could  be 
obtained,  the  submaxillary  gland  yielded  0.53  per  cent., 
the  thyroid  0.5  per  cent.,  and  the  kidneys,  spleen,  brain, 
and  muscles  under  0.5  per  cent. 

7 


98         The  Pancreas:  Its  Surgery  and  Pathology 

During  life  the  organ  is  alkaline  in  reaction,  but  it  very 
rapidly  becomes  acid  after  death ;  at  the  same  time  small 
quantities  of  tyrosin  make  their  appearance. 

Activity  of  the  pancreas  has  been  shown  by  Barcroft 
and  Starling  to  be  accompanied  by  an  increased  oxygen 
absorption,  which  is  not  due  to  the  augmented  blood- 
flow  through  the  organ.  Normally  the  oxidation  in  the 
pancreas  is  greater  than  in  the  body  generally,  being  about 
the  same  as  in  the  submaxillary  gland.  .  Increased  meta- 
bolism in  the  pancreas  has  been  found  by  Bainbridge  to  be 
accompanied  by  increased  lymph  formation,  and  he  has 
shown  that  there  is  a  close  relation  between  the  secretion 
of  pancreatic  juice  and  the  increased  flow  of  lymph. 

The  mechanism  of  the  flow  of  the  pancreatic  secretion 
was  first  satisfactorily  studied  by  Pawlow,  by  a  method 
of  obtaining  the  juice  under  practically  normal  conditions, 
which  he  described  in  1879.  In  this  method,  which 
differs  only  slightly  from  that  reported  by  Heidenhain 
in  the  following  year,  an  oval  piece  of  the  duodenal  wall 
containing  the  orifice  of  the  pancreatic  duct  is  cut  out, 
and,  after  the  lumen  of  the  bow^el  has  been  restored,  is 
brought  to  the  surface  and  stitched  into  the  slit  in  the 
abdominal  wall.  The  wound  heals  quickly,  and,  after 
two  weeks,  when  the  animals  are  ready  for  observation, 
shows  a  roundish  elevation  of  mucous  membrane  in  which 
the  cleft-like  orifice  of  the  duct  appears  about  the  centre. 
By  paying  strict  attention  to  cleanliness,  regulating  the 
diet,  and  adding  a  certain  quantity  of  sodium  bicarbonate 
to  their  food,  to  make  up  for  the  loss  of  alkali  through  the 
pancreatic  fistula,  such  animals  can  be  kept  in  good  health 
for  a  lengthy  period.  Pawlow 's  method  overcame  the 
difficulties  which  had  beset  attempts  to  investigate  the 
mechanism  and  rate  of  secretion  of  the  pancreatic  juice 
under  varying  conditions  by  previous  experimenters,  for  it 
allowed  sufficient  time  for  the  animal  to  recover  from  the 
effects  of  the  operation  and  the  transitory  interference 


Physiology  99 

with  its  functions  which  had  been  found  to  result  from 
the  formation  of  a  temporary  fistula,  while  the  inflam- 
matory changes  which  followed  the  older  methods  of 
forming  a  permanent  fistula  were  likewise  avoided. 

Employing  dogs,  provided  with  a  pancreatic  fistula 
in  this  manner,  Pawlow  investigated  the  effects  of  stimu- 
lating the  nerves  going  to  the  pancreas,  and  results  of 
variations  of  diet  upon  the  secretion.  He  found  that  if 
the  vagus  in  the  neck  be  cut  and  left  under  the  skin  for 
four  days,  so  that  the  cardiac  fibres  may  degenerate, 
stimulation  by  a  slow  induced  current,  or  by  mechanical 
blows,  causes  a  gradually  increasing  flow,  after  a  latent 
period  of  three  minutes.  When  the  stimulation  of  the 
nerve  is  discontinued  the  flow  does  not  cease  at  once, 
but  continues  in  diminishing  amount  for  four  to  five 
minutes.  This  part  of  the  experiment  can  be  done 
without  an  ansesthetic,  thus  avoiding  any  disturbing 
influences  which  might  thereby  be  introduced.  A  slow 
induced  current  was  employed,  as  it  does  not  stimulate 
the  vaso-constrictor  nerves,  excitation  of  which  would 
diminish  the  blood  supply  and  stop  the  secretion.  If 
instead  of  resecting  the  vagus  it  is  exposed  and  at  once 
stimulated  below  the  origin  of  the  cardiac  branches,  after 
the  cervical  spinal  cord  had  been  cut  to  prevent  reflexes 
from  the  sensory  nerves,  a  similar  flow  of  pancreatic 
secretion  follows.  In  this  so-called  "acute  method" 
it  was  found  that  simultaneous  stimulation  of  the  oppo- 
site vagus  often  had  an  inhibitory  action,  suppressing  the 
secretion  after  a  latent  period,  and  that  stimulation  of  the 
sympathetic  at  first  slightly  increased  the  amount  of 
secretion,  but  soon  brought  it  to  a  standstill.  As  the 
result  of  these  experiments  Pawlow  came  to  the  conclu- 
sion that  the  mechanism  of  the  pancreatic  secretion  is 
arranged  upon  the  same  plan  as  that  of  the  stomach  and 
salivary  glands,  being  determined  reflexly,  or  psychically, 
through    the    cortex   by    impulses    leaving   the    central 


loo       The  Pancreas:  Its  Surgery  and  Pathology 

nervous  system  and  travelling  by  way  of  the  vagi  and 
splanchnic  nerves  to  the  gland.  The  failure  of  Heiden- 
hain  and  other  observers  to  obtain  a  flow  of  pancreatic 
juice  on  stimulating  the  vagi  and  splanchnic  nerves  was 
attributed  by  him  to  the  unphysiological  conditions  under 
which  their  experiments  were  carried  out. 

A  pupil  of  Pawlow,  Popielski,  found  that  the  intro- 
duction of  acid  into  the  duodenum  brought  about  a  flow 
of  pancreatic  juice  after  section  of  both  vagi  and  splanch- 
nics,  or  destruction  of  the  spinal  cord,  or  complete 
extirpation  of  the  solar  plexus,  and  came  to  the  conclu- 
sion that  there  were  local  centres  presiding  over  the 
secretion  in  the  scattered  ganglia  of  the  pancreas,  and 
that,  since  there  was  no  secretion  if  the  duodenum  was 
cut  across  a  short  distance  from  the  stomach,  the  most 
important  part  was  situated  near  the  pylorus.  Wert- 
heimer  and  Lepage  confirmed  Popielski 's  observation 
with  regard  to  the  effect  of  acid  in  the  duodenum,  and 
further  reported  that  a  similar  result  followed  the  intro- 
duction of  acid  into  the  jejunum,  but  that  the  intensity 
of  the  reaction  diminished  as  the  distance  from  the  duode- 
num increased.  This  they  endeavoured  to  explain  by 
suggesting  that  the  local  centre  for  the  duodenum  lay 
in  the  pancreas,  but  that  for  the  jejunum  was  probably 
situated  in  the  solar  plexus.  These  observers,  in  their 
attempts  to  unravel  the  problem  of  the  means  by  which 
the  acid  produced  its  effect,  also  found  that  if  it  were 
injected  directly  into  the  circulation  no  secretion  of  pan- 
creatic juice  ensued. 

The  most  serious  defect  of  Pawlow's  method  of  investi- 
gation was  one  against  which  he  had  guarded  in  his 
researches  into  the  secretory  mechanism  of  the  stomach. 
In  his  experiments  upon  the  gastric  secretion  he  provided 
against  the  entry  of  food  into  the  stomach  by  an  oesopha- 
geal fistula,  but  no  provision  was  made  to  guard  against 
the  entry  of  acid  chyme  from  the  stomach  into  the  duode- 


Physiology  loi 

num  in  the  pancreatic  experiments.  This,  however,  has 
been  shown  by  the  researches  of  Bayliss  and  StarHng  to  be 
the  most  important,  if  not  the  only  stimulus  that  induces 
the  flow  of  pancreatic  juice,  Pawlow  and  his  fellow- 
workers  were  well  aware  that  the  introduction  of  dilute 
hydrochloric  acid  into  the  duodenum  brought  about  active 
secretion,  so  much  so  in  fact  that  they  made  use  of  it  as  a 
crucial  test  for  deciding  the  normal  relation  of  the  alimen- 
tary canal  to  the  pancreas,  but  their  minds  were  so  imbued 
with  the  idea  of  a  nervous  control  that  they  failed  to 
recognize  the  true  importance  of  their  own  observations 
in  this  direction.  They  attributed  the  result  produced 
by  the  acid  to  excitation  of  the  peripheral  nerve-endings 
in  the  mucous  membrane  of  the  intestine.  A  second 
hypothesis  considered  by  Pawlow,  only  to-be  rejected, 
was  that  the  acid  was  absorbed  into  the  blood  and  carried 
to  the  secretory  centres  or  gland  cells,  where  it  acted 
as  a  stimulant  for  the  production  of  the  secretion.  His 
reasons  for  setting  aside  this  explanation  were  that  if  it 
were  correct,  the  alkalinity  of  the  blood  would  be  dimin- 
ished during  digestion  and  not  increased,  as  it  is  known 
to  be;  further,  that  experiment  shows  that  when  acid 
solutions  are  injected  into  the  rectum  the  pancreas 
remains  at  perfect  rest,  and  in  the  same  way  acids  do  not 
act  upon  the  pancreas  so  long  as  they  remain  in  the 
stomach. 

A  third  explanation  has  been  offered  by  Bayliss  and 
Starling  and  supported  by  convincing  experimental 
evidence.  After  setting  aside  the  nervous  theory,  by 
proving  that  the  presence  of  hydrochloric  acid  in  a  liga- 
tured loop  of  the  upper  part  of  the  jejunum,  the  nervous 
connections  of  which  had  been  completely  destroyed, 
brought  about  a  copious  flow  of  pancreatic  juice,  and, 
accepting  the  observations  of  Wertheimer,  that  the  intro- 
duction of  acid  into  the  blood  failed  to  excite  secretion, 
they  concluded  that  the  acid  must  act  upon  the  cells  of 


I02       The  Pancreas:  Its  Surgery  and  Pathology 

the  intestinal  mucous  membrane  and  produce  some  sub- 
stance which,  being  absorbed  into  the  blood,  travels  to 
the  pancreatic  cells  and  arouses  them  to  activity.  To 
prove  this  they  scraped  off  the  cells  lining  the  mucous 
membrane  of  the  upper  part  of  the  jejunum,  rubbed  them 
up  in  a  mortar  with  sand  and  0.4  per  cent,  hydrochloric 
acid,  filtered  the  extract,  and  injected  the  filtrate  into  a 
vein.  The  result  was  a  brilliant  confirmation  of  their 
surmise,  for  a  flow  of  pancreatic  juice  was  produced  which 
was  even  greater  than  that  excited  by  the  introduction 
of  acid  into  the  lumen  of  the  intestine.     This  effect  was 


Fig.  48. — The  efifects  produced  by  the  injection  of  acid  into  a  loop 
of  small  intestine  after  destruction  of  the  nerves:  a,  Blood  pressure; 
b,  drops  of  pancreatic  juice;  c,  signal  marking  injection  of  50  c.c.  of 
0.4  per  cent.  HCl;  d,  time  in  ten  minutes  (Starling). 


found  not  to  be  specific,  for  an  extract  prepared  from  the 
upper  part  of  the  intestine  of  any  vertebrate  animal 
induced  pancreatic  secretion  in  the  same,  or  any  other, 
species  into  which  it  was  injected.  The  activity  of  the 
extract  prepared  from  various  parts  of  the  intestine  was 
shown  to  diminish  as  the  distance  from  the  pylorus  was 
increased,  that  from  the  duodenum  being  most  active 
and  that  from  the  lower  part  of  the  ileum  being  entirely 
ineffective,  thus  agreeing  with  the  observations  of  Wert- 
heimer  and  Lepage  on  the  secretory  activity  induced  by 
the  introduction  of  acid  into  various  parts  of  the  gut. 
The   chemical  messenger,   or  harmone,   which  brings 


Physiology  103 

about  this  reaction,  and  to  which  its  discoverers  have 
given  the  name  of  ''secretin,''  has  not  been  isolated. 
Once  formed  by  the  action  of  acid,  or  boiling  water,  on 
the  intestinal  mucous  membrane,  it  can  be  boiled,  showing 
that  it  is  not  a  ferment,  neutralised  or  made  alkaline, 
without  being  destroyed.  It  is  readily  oxidized,  is  not 
precipitated  by  the  ordinary  reagents  for  proteids,  but 
is  soluble  in  90  per  cent,  alcohol  in  the  presence  of  ether, 
although  it  is  insoluble  in  absolute  alcohol  and  ether. 


Pig  45. — Effects  produced  by  the  injection  of  secretin  prepared 
from  the  intestinal  mucous  membrane:  a,  Blood  pressure;  6,  drops  of 
pancreatic  juice;  c,  signal  marking  injection  of  secretm;  d,  time  m  ten 
minutes  (Starling). 

It  is  diffusible  through  animal  membranes,  and  can  be 
filtered  through  a  gelatinised  Chamberland  filter.  It 
is  not  precipitated  by  tannic  acid,  thus  excluding  bodies 
of  an  alkaloidal  nature  and  di-amido  compounds.  This 
evidence  points  to  secretin  being  a  body  of  relatively 
small  molecular  weight,  and  not  a  colloid.  It  may  be 
compared  to  the  active  principle  of  the  suprarenal  gland, 
adrenalin,  which  has  been  obtained  in  a  crystalline  form 
and  the  chemical  constitution  of  which  has  been  deter- 
mined.    This  is  indeed  what  might  be  expected  of  a 


I04      The  Pancreas :  Its  Surgery  and  Pathology 

substance  which  has  to  be  turned  out  into  the  blood  at 
repeated  intervals  in  order  to  produce  in  some  distant 
organ  a  physiological  response  proportional  to  the  dose. 

Even  after  coagulation  of  the  mucous  membrane  by 
heat  or  alcohol,  secretin  can  be  extracted  by  the  action 
of  warm  dilute  acid,  but  mere  extraction  with  water  or  al- 
cohol, in  which  secretin  is  freely  soluble,  does  not  give 
an  active  solution.  It  is  therefore  concluded  that  the 
epithelial  cells  contain  a  precursor  of  secretin,  which  is 
insoluble  in  water,  alcohol,  and  salt  solution,  termed 
''prosecretin,''  and  that  this,  on  hydrolysis  with  acids, 
gives  rise  to  the  active  substance.  It  has  been  found 
impossible  to  prepare  secretin,  or  a  substance  having  a 
similar  action  on  the  pancreas,  from  any  organ  or  tissue 
of  the  body  other  than  the  mucous  membrane  of  the  duo- 
denum and  the  jejunum.  The  effect  of  secretin  appears  to 
be  limited  to  the  pancreas  and  liver,  for  while  a  solution, 
free  from  bile  salts,  on  injection  into  a  vein  induces  a 
marked  flow  of  pancreatic  juice  and  some  increase  in  the 
excretion  of  bile,  it  is  found  to  have  no  action  upon  any 
other  gland.  Bayliss  and  Starling  believe  that  it  acts 
as  a  direct  chemical  stimulant  to  the  secretory  cells  of 
the  pancreas,  since  the  flow  of  secretion  is  still  obtained 
when  the  gland  has  been  cut  off,  as  far  as  possible,  from 
all  nervous  connections. 

The  question  as  to  whether  secretin  can  be  produced 
from  the  mucous  membrane  of  the  upper  part  of  the 
small  intestine  by  any  other  substance  than  hydrochloric 
acid,  which  is  undoubtedly  the  most  effective,  has 
received  attention  at  the  hands  of  several  observers. 
Fats  were  believed  by  Pawlow  to  be  independent  exci- 
tors  of  the  pancreatic  flow,  for  he  pointed  out  that,  since 
they  restrain  the  secretion  of  gastric  juice,  the  output 
of  pancreatic  juice  which  follows  their  administration 
is  not  likely  to  be  indirectly  due  to  acid  in  the  gastric 
contents.     Oil  when  rubbed  up  with  duodenal  mucous 


Physiology  105 

membrane  does  not  give  rise  to  secretin,  but  Fleig  has 
shown  that  if  a  solution  of  soap  is  employed  instead,  the 
mixture,  on  injection  into  the  blood  stream,  gives  rise 
to  active  pancreatic  secretion.  It  is  therefore  possible 
that  fats  owe  their  activity  as  excitors  of  the  pancreatic 
secretion  to  the  formation  of  a  certain  amount  of  soap 
in  the  intestine,  which  in  its  turn  sets  free  secretin.  Fleig 
regards  the  secretin  produced  by  the  action  of  soap  as 
different  from  that  formed  by  acid,  and  has  named  it 
"sapocrinin,"  but  there  is  no  evidence  to  justify  such  a 
conclusion. 

Irritating  substances  such  as  oil  of  mustard,  or  ether, 
do  not  produce  secretin  from  the  scraped-off  mucous 
membrane  (Starling),  but  they  produce  a  flow  of  pancre- 
atic juice  on  being  introduced  into  a  loop  of  small  intestine, 
which  Wertheimer's  experiments  show  is  due  to  the 
presence  of  secretin  in  the  blood.  Starling  explains  this 
by  supposing  that  the  secretin  is  formed  by  a  process  of 
hydrolysis  in  the  over-stimulated  cells  of  the  intestine, 
possibly  as  a  stage  in  their  death. 

Most  investigators  have  admitted  that  secretin  is  the 
most  important  exciter  of  the  pancreatic  secretion,  but 
there  are  some  who  still  believe  that  nervous  activity 
plays  some  part  in  the  process.  Starling  considers  it 
doubtful  whether  the  vagus  has  any  direct  secretory 
action  on  the  cells  of  the  pancreas,  and  points  out  that 
the  normal  effect  of  stimulating  the  vagus  is  to  bring 
about  movements  of  the  stomach,  which  may  cause  its 
contents  to  flow  into  the  duodenum,  and  there  set  up  the 
chemical  mechanism  of  secretion  which  he  and  Bayliss 
discovered.  When  due  precautions  are  taken  to  prevent 
the  stomach  contents  passing  into  the  intestine,  stimula- 
tion of  the  vagus  produces  such  a  slight  flow  from  the 
pancreatic  duct  that  it  can  hardly  be  regarded  as  evidence 
of  the  presence  of  secretory  fibres  in  the  nerve.     Some 


io6       The  Pancreas:  Its  Surgery  and  Pathology 

observations  on  the  pancreatic  secretion  in  a  man  have 
been  described  by  Clayton-Greene,  which  he  thinks 
support  Pawlow's  original  theory  that  secretion  is  in- 
fluenced by  a  nervous  mechanism.  The  case  was  one  in 
which,  during  pylorectomy  for  malignant  disease  of  the 
stomach,  a  portion  of  the  pancreas  was  torn  across,  and 
three  days  later  a  pancreatic  fistula  •  formed.  Food 
given  by  the  mouth  was  followed,  some  few  seconds  after 
it  had  been  swallowed,  by  a  definite  secretion  of  pancre- 
atic juice,  and  the  sight  of  food  was  also  found  to  set  up 
secretion.  He  considers  that  the  conditions  under  which 
the  flow  started  were  such  that  it  could  not  be  explained 
as  the  result  of  the  formation  and  absorption  of  secretin, 
and  that  in  the  observations  made  in  this  case  there  was 
support  for  the  theory  that  stimulation  of  a  sensory 
nerve  could  evoke  a  secretion  from  the  pancreas  as  it 
does  from  the  salivary  glands. 

The  composition  and  characters  of  the  external  secre- 
tion of  the  pancreas  have  been  chiefly  studied  in  dogs. 
That  obtained  by  inserting  a  cannula  into  the  duct  two 
or  three  hours  after  a  meal  is  found  to  be  a  clear,  odour- 
less, colourless,  syrupy  fluid  of  a  strongly  alkaline  reaction 
and  a  specific  gravity  of  about  1.030.  It  contains  from 
2  to  15  per  cent,  of  solid  matter,  of  which  a  variable,  but 
often  considerable,  proportion  is  coagulable  proteid. 
The  alkalinity,  which  is  equal  to  0.2  to  0.4  per  cent,  of 
sodium  hydrate,  is  generally  said  to  be  due  to  carbon- 
ates and  phosphates  of  sodium.  Alkaline  chlorides,  and 
small  quantities  of  calcium  and  magnesium  phosphates, 
leucin,  fat,  and  soaps  are  also  present.  The  fluid  readily 
decomposes  on  exposure  to  the  air.  The  following  analy- 
ses of  the  temporary  secretion,  obtained  directly  after 
operation  by  Schmidt,  show  that  in  the  same  form  of 
fistula  the  proportion  of  total  solids  varies  very  considera- 
bly: 


Physiology 


107 


(a) 

(«) 

Water 

900.8 

99.2 

90.4 

8.8 

884.4 
115. 6 

Total  solids 

Organic  matter 

Ash 

The  secretion  from  a  permanent  fistula,  collected  a 
few  hours  to  several  days  after  the  operation,  resembles 
that  from  a  temporary  fistula  in  its  general  characters, 
but  is  poorer  in  solids  and  coagulable  proteid.  It  con- 
tains from  1.5  to  3.5  per  cent,  of  the  former  and  0.5  to 
2.5  per  cent,  of  the  latter.  The  specific  gravity  is  also 
less,  being  generally  about  i.oio  to  i.oii.  Schmidt's 
analyses  of  three  specimens  gave  the  following  results : 


(.a) 

W 

(c) 

Water 

976.8 

23.2 

16.4 

6.8 

979-9 
20.1 
12.4 

7-5 

984.6 
15-4 

Total  solids 

Organic  matter 

Ash 

9.2 
6.1 

Starling  states  that  the  juice  from  a  permanent  fistula, 
after  feeding,  is  similar  in  all  respects  to  that  flowing 
from  a  temporary  fistula  as  the  result  of  injecting  secretin, 
or  introducing  acid  into  the  duodenum.  According  to 
him,  it  is  a  somewhat  viscid,  clear,  colourless  fluid,  of 
a  specific  gravity  of  about  1.030,  and  contains  from  2 
to  3.5  per  cent,  of  total  solids.  About  i  per  cent,  of  the 
solid  consists  of  salts  and  the  remainder  of  coagulable 
proteid.  It  is  always  strongly  alkaline,  10  c.c.  of  the 
juice  requiring  from  10  to  15  c.  c.  of  decinomal  acid  to 
neutralise  it.  That  is  to  say,  its  alkalinity  is  equivalent  to 
from  0.365  to  0.547  per  cent,  of  hydrochloric  acid,  figures 
which  correspond  closely  to  the  acidity  of  the  gastric 
juice  (0.48  per  cent.).  A  certain  proportion  of  the  pro- 
teid is  precipitated  on  neutralisation.     In  neutral  solu- 


io8       The  Pancreas:  Its  Surgery  and  Pathology 

tion  about  half  the  total  proteid  is  coagulable  at  between 
55°  and  60°  C,  the  remainder  coagulating  at  about  75°  C. 

Opportunities  for  studying  human  pancreatic  juice  are 
rare,  and  even  in  such  cases  as  have  occurred  the  material 
can  hardly  be  regarded  as  normal,  for  it  has  usuall}^  been 
either  the  contents  of  a  cyst  or  the  drainings  from  a  wound. 
In  a  case  where  the  entry  of  the  secretion  into  the  intestine 
was  prevented  by  the  pressure  of  a  malignant  growth 
upon  the  duct  of  Wirsung,  Herter  found  that  it  was  a 
clear,  alkaline  fluid,  without  odour,  and  contained  2,41 
per  cent,  of  solids,  of  which  0.64  per  cent,  was  soluble 
in  alcohol.  He  separated  1.15  per  cent,  of  peptone 
(and  enzymes),  but  no  other  proteid,  and  0.62  per  cent, 
of  mineral  substances.  The  ash  was  found  to  be  very 
rich  in  alkaline  phosphates.  Zawadsky  analysed  the 
pancreatic  secretion  of  a  young  woman  with  a  fistula 
that  remained  after  a  cyst  of  the  pancreas,  and  found 
864.05  p.m.  of  water,  132.51  p.m.  of  organic  matter, 
and  3.44  p.  m.  of  inorganic  substances.  The  quantity  of 
proteid  was  92.05  p.  m.  The  investigations  reported 
by  Glaessuer,  on  a  case  operated  on  by  Korte,  in  which 
the  pancreatic  duct  and  common  bile-duct  were  drained 
for  eight  days  after  an  operation  undertaken  to  relieve  a 
simple  stricture  of  the  bile-passage  following  duodenal 
ulcer,  will  be  referred  to  later,  when  the  functions  of  the 
pancreatic  juice  are  considered,  but  it  may  be  mentioned 
here  that  the  fluid  was  clear,  alkaline  in  reaction,  and  of  a 
specific  gravity  of  1.007.  It  contained  6  per  cent,  of 
ash  and  15  per  cent,  of  proteid,  of  which  more  than  half 
was  albumin. 

Different  observers  vary  considerably  in  their  esti- 
mate of  the  total  daily  output  of  pancreatic  juice.  Bidder 
and  Schmidt  state  that  the  dog,  under  normal  condi- 
tions, secretes  2.5  grams  per  kilo  of  body-weight  a  day, 
while  Pawlow  gives  21,8  c.  c.  per  kilo  as  the  normal  out- 
put for  twenty-four  hours.     On  the  basis  of  Bidder  and 


Physiology  109 

Schmidt's  findings  an  average  man  of  154  pounds  weight 
might  be  expected  to  secrete  175  grams  of  pancreatic 
juice  a  day,  but  in  Glaessuer's  case  the  daily  amount 
collected  was  from  500  to  800  c.c,  and  in  Wohlgemuth's 
400  c.c.  It  is  generally  assumed  that  the  amount  lies 
between  200  and  500  c.c. 

Excepting  in  herbivora,  such  as  the  rabbit,  in  which 
digestion  is  uninterrupted,  the  secretion  of  pancreatic 
juice  is  intermittent.  In  a  dog  with  a  pancreatic  fistula 
there  is  no  secretion  while  the  animal  is  fasting,  but  the 
administration  of  food,  or  even  the  sight  of  food,  brings 
about  a  flow,  after  a  latent  period  of  two  to  three  minutes. 
The  flow  of  secretion  induced  by  a  meal  gradually  in- 
creases in  amount  until  it  reaches  a  maximum  in  two  to 
three  hours;  it  then  diminishes,  the  lowest  reading  being 
reached  in  five  to  seven  hours ;  a  second  rise,  reaching  its 
maximum  in  the  ninth  to  the  eleventh  hour,  may  then 
take  place,  after  which  it  again  gradually  sinks  until  it 
finally  stops  about  the  eighteenth  to  the  twentieth  hour, 
unless  a  fresh  supply  of  food  is  ingested.  Both  the  amount 
and  rate  of  secretion  have  been  shown  by  Pawdow  to 
vary  with  the  nature  of  the  food,  Walther,  working 
in  Pawlow's  laboratory,  found  that,  taking  the  hourly 
quantity  of  pancreatic  juice  poured  out  for  corresponding 
nitrogen  equivalents  of  flesh,  bread,  and  milk,  the  follow- 
ing results  were  obtained : 

With  100  grams  of  flesh  .   .  .   .38.7     44.6     30.4      16.9       0.8 131.45  c.c. 

With  250  grains  of  bread    .   .   .  36.5     50.2      20.9      14. i      16.4     12.7     10.7     6.9       168.4    c.c. 
With  600  c.c.  of  milk 8.5       7.6      14.6      11. 2       3.3       i.o      .   .       .   .         46.1    c.c. 

When  these  results  are  plotted  out  in  curves  the  varia- 
tions in  amount  and  rate  of  secretion  induced  by  the 
food  materials  experimented  with  are  well  seen  (Fig,  50), 

Wohlgemuth,  working  with  a  patient  with  a  pancreatic 
fistula  the  result  of  an  operation  after  injury  of  the 
pancreas,  also  found  that,  employing  fixed  quantities  of 
food  and  collecting  the  juice  from  hour  to  hour,  the  quanti- 


no       The  Pancreas:  Its  Surgery  and  Patholog}' 

tity  secreted  was  greater  with  carbohydrates,  smaller 
with  albumin,  and  least  with  fats.  The  secretion  was 
usually  most  active  in  the  second  hour. 

According  to  the  secretin  theory,  the  variations  pro- 
duced by  different  classes  of  food  material  are  not  due, 
as   Pawlow   supposed,   to   some   specific   influence   they 


V.Hi'ir     '' I  II  HI  IV  V   1  iiiiiiv  vvivnvirn  niniv  v  v; 


IsBshasssssssBSi 

■■■r~ 


Resh,  100  grins.         Ifru.-ul, 'irrf)  j-nns.  \ 


Fig.  50. — Curves  of  secretion  of  pancreatic  juice  after   100  grams  of 
flesh;  250  grams  of  bread;  600  c.c.  of  milk  (Pawlow). 


exert  upon  the  pancreas  by  way  of  its  nerve  supply, 
but  upon  the  acidity  of  the  chyme  and  its  rate  of  dis- 
charge into  the  intestine.  The  first  portion  of  the  acid 
stomach  contents  passed  into  the  duodenum  will  continue 
to  excite  the  formation  of  secretin  from  the  epithelial 
cells  until  the  alkaline  pancreatic  juice,  secreted  in  re- 


Physiology  1 1 1 

sponse  to  its  stimulating  effect,  has  completely  neutra- 
lized the  acid;  a  second  supply  of  chyme  will  then  be 
ejected  by  the  stomach,  giving  rise  in  its  turn  to  the 
formation  of  secretin  and  of  an  alkaline  pancreatic  juice 
by  which  it  will  be  neutralised,  and  this  process  will  he 
continued  so  long  as  the  products  of  the  activities  of  the 
stomach  continue  to  pass  into  the  intestine.  As  a  cer- 
tain amount  of  bile  is  secreted  at  the  same  time  as  the 
pancreatic  juice,  and  the  secretions  of  the  intestine  are 
also  alkaline,  a  somewhat  smaller  quantity  of  pancreatic 
juice  will  be  formed  than  would,  by  itself,  be  sufficient 
to  neutralise  the  acid  contents  of  the  stomach. 


Fig.  51. — Effects  of  the  injection  of  secretin  on  the  flow  of  pan- 
creatic juice  and  bile:  a,  Blood  pressure;  b,  drops  of  pancreatic  juice; 
c,  drops  of  bile;  d,  signal  marking  injection  of  secretin;  e,  time  in  ten 
minutes  (Starling). 

Ferments. — The  pancreatic  juice  contains  four,  or  pos- 
sibly five,  ferments  or  digestive  enzymes:  (i)  "Amylop- 
sin,"  or  pancreatic  diastase,  a  diastatic  ferment  which 
converts  starch  and  glycogen  into  dextrin  and  maltose, 

(2)  "Trypsin,"  a  proteolytic  ferment  which  converts 
proteids    into    albumoses,    peptone,     and    amino-acids. 

(3)  "Steapsin,"  or  "pialyn,"  a  steatolytic,  lipolytic,  or 
fat-splitting  ferment,  Avhich  converts  neutral  fats  into 
fatty  acids  and  glycerine.  (4)  A  milk-curdling  ferment, 
which  in  the  presence  of  calcium  salts  changes  caseinogen 
into  casein;  and,  possibly,  (5)  a  ferment  which  has  been 
named  "lactase,"  because  of  its  supposed  power  of  split- 
ting milk-sugar  into  galactose  and  dextrose. 

The  collective  pancreatic  ferments  are  thus  capable 


112       The  Pancreas:  Its  Surgery  and  Pathology 

of  acting  upoh  all  forms  of  food-stuffs  and  carrying  to  a 
final  issue  the  changes  commenced  by  other  digestive 
glands.  The  same  ferments  are  found  in  the  pancreatic 
secretions  of  all  vertebrates,  but  in  the  human  subject, 
although  trypsin  is  present  during  the  last  third  of  foetal 
life,  the  diastatic  ferment  does  not  make  its  appearance 
until  a  month  or  more  after  birth. 

The  process  of  digestion  of  starches  commences  in  the 
mouth  through  the  agency  of  the  ptyalin  of  the  saliva, 
but  it  is  quickly,  although  not  immediately,  stopped  in 
the  stomach  through  the  precipitation  of  the  diastatic 
ferment  by  the  gastric  juice.  In  the  intestine  the  amy- 
lopsin  of  the  pancreatic  secretion  continues  the  process, 
but  much  more  vigorously  and  rapidly,  exerting  some 
action  even  upon  unboiled  starch.  The  main  results  of 
the  activity  of  the  two  ferments  are  the  same,  however — - 
namely,  dextrin  and  maltose.  Only  small  quantities  of 
dextrose  are  produced,  even  by  the  action  of  the  more 
vigorous  pancreatic  ferments.  The  final  conversion  to 
this  substance  is  brought  about  either  through  the  activ- 
ity of  epithelium  of  the  intestinal  wall  or,  possibly,  by 
the  action  of  a  special  ferment  in  the  pancreatic  juice, 
to  which  the  name  "maltase"  has  been  given.  The 
diastatic  ferment  of  the  pancreatic  juice  acts  most  satis- 
factorily at  a  temperature  of  30°  to  45°  C.  in  a  neutral 
or  very  faintly  acid  medium.  The  optimum  reaction, 
according  to  Melzer,  is  about  0.0 1  per  cent,  of  hydro- 
chloric acid.  It  is  quickly  destroyed  by  strong  mineral 
acids  and  its  action  is  suspended  by  0.05  per  cent,  of 
lactic  acid  or  0.08  per  cent,  of  acetic  acid  (Hofmeister) . 

Although  Claude  Bernard  discovered  the  digestive 
powers  of  pancreatic  juice  upon  proteids,  he  believed 
that  the  presence  of  bile  was  necessary,  and  it  was  not 
until  Coivisart,  in  1857,  demonstrated  that  the  juice  alone 
exerted  a  powerful  solvent  action  at  the  temperature  of 
the  body,  and  that  infusions  of  the  fresh  gland  possessed 


Physiology  113 

the  same  property,  that  our  knowledge  of  this  function 
of  the  pancreas  was  placed  on  a  secure  footing.  The 
latter  observer  also  showed  that  the  products  of  the 
pancreatic  digestion  of  proteids  had  the  same  general 
characters  as  those  resulting  from  the  action  of  gastric 
juice.  In  1877,  Kiihne  carried  the  investigations  a  step 
further  by  excluding  the  effects  of  bacterial  action,  of 
which  account  had  not  been  taken  by  previous  experi- 
menters. He  found  that  the  addition  of  a  small  quantity 
of  salicylic  acid  to  a  pancreatic  digestion-mixture  pre- 
vented the  growth  of  micro-organisms  but  did  not  stop 
the  digestive  process.  He  therefore  concluded  that  the 
action  was  due  to  an  enzyme  and  named  it  "trypsin^ 
It  is  now  known  that  the  pancreatic  juice  does  not  con- 
tain trypsin  but  trypsinogen,  and  that  it  is  by  the  action 
of  a  substance  contained  in  the  succus  entericus,  known 
as  "  enter okinase,"  on  the  latter  that  the  active  ferment 
is  produced.  Different  views  are  held  as  to  the  natiore  of 
enterokinase.  By  its  discoverers,  Pawlow  and  Schepo- 
walnikow,  it  is  regarded  as  a  "ferment  of  ferments,"  and 
in  this  they  are  supported  by  Starling,  but  Delezenne, 
and  others  of  the  French  school,  consider  that  it  is  rather 
of  the  nature  of  an  amboceptor  binding  the  ferment  to 
the  proteid,  Delezenne  has  recently  stated  that  inactive 
pancreatic  juice  acquires  an  extremely  powerful  proteo- 
lytic action  on  being  incubated  for  several  hours  with  a 
suitable  quantity  of  a  soluble  calcium  salt ;  barium,  stron- 
tium, and  magnesium  have  little  or  no  effect  and  the  ac- 
tion of  lime  salts  in  this  respect  is  specific.  Julius  Wohlge- 
muth has  also  shown  that  the  trypsinogen  contained  in 
the  juice  from  a  fistula  is  activated  by  glycine,  alanine,  and 
leucine,  and  feebly  by  tyrosine. 

Schiff,  Herzen,  Gachet,  and  Pochon  have  maintained 
that  the  spleen  is  of  importance  in  the  production  of 
trypsin,  but  their  conclusions  have  been  disputed  by 
Ewald  and  Heidenhain,  and  are  not  generally  accepted. 


114       The  Pancreas:  Its  Surgery  and  Pathology 

The  proteolytic  ferment  of  the  pancreatic  juice  can  act 
in  an  alkaline,  neutral,  or  faintly  acid  medium.  The 
optimum  is  about  i  per  cent,  of  sodium  carbonate,  other 
alkaline  carbonates  being  found  to  be  much  less  effective. 
Its  action  is  prevented  by  the  presence  of  free  mineral 
acids,  even  in  small  quantities.  Free  hydrochloric  acid 
destroys  the  ferment  more  rapidly  if  pepsin  is  also  present, 
but  hydrochloric  acid  combined  with  albumin,  in  not  too 
large  amounts,  appears  to  rather  increase  the  rapidity 
of  its  action.  Organic  acids  exert  a  much  less  harmful 
effect  than  mineral  acids,  and  it  is  said  that  in  the  presence 
of  0,2  per  cent,  of  lactic  acid,  bile,  and  salt,  the  proteolytic 
action  is  very  energetic.  According  to  Wohlgemuth, 
the  tryptic  activity  of  pancreatic  juice  is  doubled  by  the 
presence  of  bile.  Small  quantities  of  salicylic  acid  have 
no  effect,  and  only  saturated  solutions  interfere  with  its 
activity.  The  nature  of  the  proteid  also  exerts  some 
influence  on  the  ease  with  which  the  digestive  process 
proceeds ;  fresh  unboiled  fibrin  is  attacked  and  dissolved 
exceedingly  rapidly,  but  boiled  fibrin  or  coagulated  white 
of  egg  are  digested  much  more  slowly,  hence  it  is  advisa- 
ble to  employ  one  or  other  of  the  latter  when  testing  the 
digestive  power  of  a  fluid  containing  pancreatic  ferments. 
The  optimum  temperature  for  the  action  of  trypsin  lies 
between  30°  and  45°  C.  Beyond  that  its  digestive  power 
rapidly  increases  up  to  60°  C,  but  the  ferment  is  at  the 
same  time  quickly  destroyed  and  loses  its  power,  so 
that  at  75°  to  80°  C.  it  ceases  altogether. 

On  exposing  a  proteid  to  the  action  of  activated  pan- 
creatic juice  it  is  found  to  be  attacked  and  eroded  from 
the  outside,  without  undergoing  any  swelling,  or  becom- 
ing clearer,  as  in  gastric  digestion.  The  alkali  albumin 
first  formed,  when  the  digestion  takes  place  in  an  alkaline 
medium,  is  quickly  converted  into  deuteroalbumose ; 
this  in  turn  gives  rise  to  peptone,  and  from  this  again 
various   amino-acids,  and   relatively  simple   nitrogenous 


Physiology  115 

bodies,  are  derived.  No  proto-albumose  or  hetero- 
albumose  can  be  detected,  as  in  the  earher  stages  of  gas- 
tric digestion,  probably  because  the  action  of  trypsin  is 
so  much  more  rapid  and  energetic  than  that  of  pepsin 
that  these  bodies  are  broken  down  as  quickly  as  they  are 
formed.  Kiihne  as  the  result  of  his  work  on  digestion 
considered  that  the  peptone  formed  in  the  stomach 
differed  from  that  produced  in  pancreatic  digestion. 
The  former  he  named  "amphopeptone,"  because  he 
believed  that  it  consisted  of  two  united  groups  ("hemi- 
peptone,"  which  could  be  broken  down  by  trypsin  into 
simpler  bodies,  and  "antipeptone,"  which  was  resistant 
to  the  action  of  trypsin) ;  the  latter,  he  stated,  consisted 
only  of  "antipeptone."  Kiihne  himself,  however,  had 
doubts  as  to  the  unity  of  antipeptone,  and  it  has  now  been 
shown  that  it  is  really  a  mixture  of  various  amino-acids 
and  hexone  bases.  Emil  Fischer,  working  at  the  cleav- 
age products  of  proteid  digestion,  has  isolated  com- 
binations of  amino-acids,  which  he  terms  "polypeptides," 
occupying  an  intermediate  position  between  the  pro- 
teoses and  peptones,  on  the  one  hand,  and  the  final 
products  of  digestion  on  the  other.  It  is  now  generally 
accepted  that  "ampho-peptone,"  "hemi-peptone,"  and 
"anti-peptone,"  in  the  sense  used  by  Kiihne,  do  not  exist, 
and  that  there  is  no  essential  difference  between  the  prod- 
ucts of  the  activity  of  trypsin  and  of  pepsin.  Both  split 
up  the  proteid  molecule  by  a  process  of  hydrolysis  into 
simpler  combinations  of  a  similar  nature,  but  while  the 
whole  series  of  processes  is  rapidly  and  easily  performed 
by  the  powerful  tryptic  ferment,  the  gastric  juice  only 
acts  completely  upon  a  variable  fraction,  which  can  be 
broken  off  with  comparative  ease.  The  small  quantities 
of  leucine,  tyrosine,  and  other  bodies  of  low  molecular 
weight,  now  known  to  be  formed  during  gastric  digestion, 
are  what  were  grouped  together  by  Kiihne  as  anti-peptone. 
The    only   essential    difference,    therefore,    between   the 


ii6       The  Pancreas:  Its  Surgery  and  Patdology 

proteolytic  activity  of  trypsin   and  pepsin  is   in  their 
velocity  of  action. 

It  was  formerly  believed  that  the  leucine,  tyrosine, 
and  similar  bodies  of  relatively  simple  composition  pro- 
duced during  the  digestion  of  proteids,  were  merely  waste 
substances  formed  by  the  excessive  activity  of  the  pan- 
creatic juice,  which  were  normally  conveyed  to  the  liver 
and  there  rapidly  destroyed,  but  evidence  is  now  rapidly 
acciunulating  which  tends  to  show  that  the  main  part  of 
the  proteid  taken  in  as  food  is  broken  up  into  these  simple 
cleavage  products  before  it  is  absorbed,  and  that  the  body 
proteids  are  built  up  synthetically  from  them.  That  it  is 
possible  to  maintain  the  weight,  health,  and  nitrogenous 
equilibritun  of  animals  by  feeding  them  on  the  crystalline 
cleavage  products  of  the  pancreatic  digestion  of  proteids 
has  been  experimentally  demonstrated  by  Loewi  and 
others,  and  the  probability  that  such  is  the  natural  pro- 
cess by  which  proteids  are  absorbed  does  away  with  the 
difficulty  of  explaining  how  the  constant  chemical  compo- 
sition of  the  various  tissues  of  the  body  is  maintained  in 
spite  of  the  widely  differing  nature  of  the  food  materials 
from  which  they  are  derived. 

Fresh  pancreatic  juice,  which  has  not  been  activated 
by  enterokinase,  possesses  slight  digestive  powers  for 
proteids.  This  action,  which  is  quite  distinct  from  that 
due  to  trypsin,  is  akin  to  the  feeble  proteolytic  property 
possessed  by  many  animal  tissues,  particularly  the  kidney 
(Vernon) . 

Cohnheim  has  demonstrated  the  presence  of  a  ferment 
in  the  succus  entericus  of  the  dog,  which  has  the  property 
of  splitting  proteoses  and  peptone  into  simpler  products, 
but  has  no  action  on  native  proteids,  and  to  it  he  attaches 
considerable  importance.  According  to  Kutscher,  how- 
ever, it  is  a  comparatively  feeble  and  unimportant 
ferment.  To  this  intestinal  enzyme  Cohnheim  gave  the 
name  of  "  erepsin,"  but  the  same  term  has  also  been  used 


Physiology  117 

by  Starling  to  describe  the  proteolytic  ferment  met  with 
in  fresh  pancreatic  secretion  and  in  the  tissue  juices  gen- 
erally. A  similar  ferment,  found  in  the  intestinal  juice 
of  suckling  infants,  may  possibly  be  of  value,  as  it  is  said 
to  speedily  break  up  caseinogen  into  casein. 

Collagen,  the  chief  constituent  of  connective  tissue, 
is  not  acted  upon  by  pancreatic  juice,  unless  it  has  pre- 
viously been  boiled  with  water,  or  has  been  acted  upon 
by  dilute  acid,  hence  connective  tissue  is  not  digested  if 
the  stomach  has  been  removed,  or  if  the  secretion  of  acid 
is  interfered  with  by  disease.  Gelatin  ingested  as  such, 
or  derived  by  previous  digestive  changes  from  collagen, 
is  converted  by  trypsin  into  gelatin-peptones.  Elastin 
is  attacked  and  dissolved.  Mucin  and  nucleo-proteids, 
after  a  preliminary  cleavage  into  their  constituent  pro- 
teids  and  organic  radicles,  undergo  digestive  changes  in 
the  pancreatic  secretion.  In  the  fasting  animal  a  mix- 
ture of  pancreatic  juice  with  the  intestinal  secretions  is 
said  to  exert  an  exceedingly  powerful  action  upon  the 
wall  of  the  intestine,  giving  rise  to  extensive  inflammatory 
changes  and  erosions  (Starling). 

The  digestion  of  fat  is  peculiarly  a  function  of  the 
pancreatic  juice.  Neutral  fats  are  entirely  unaffected  by 
the  secretions  of  the  salivary  glands,  and  in  the  stomach 
are  only  slowly  changed,  yielding  but  i.o  to  2.7  per  cent, 
of  fatty  acid  after  some  hours.  Fine  emulsions  of  fat, 
such  as  occur  in  the  yolk  of  eggs  and  in  milk,  may  be 
more  completely  digested,  however,  for  Volhard  found 
that  the  former,  after  one  to  four  hours'  stay  in  the  stom- 
ach, might  contain  as  much  as  78  per  cent,  of  free  fatty 
acid,  a  fact  probably  of  some  practical  importance  in 
young  infants  before  the  lipolytic  function  of  the  pan- 
creatic secretion  is  fully  developed,  and  in  adult  patients 
whose  pancreas  is  disorganised  by  disease.  The  fat- 
splitting  power  of  the  stomach  is  believed  to  be  due  to  a 
gastric  lipase,  although  it  has  also  been  attributed  to  the 


ii8       The  Pancreas:  Its  Surgery  and  Pathology 

action  of  bacteria.  No  fat-splitting  ferment  has  been 
obtained  from  the  intestinal  mucous  membrane  or  from 
the  chyle. 

Eberle,  in  1834,  was  the  first  to  observe  that  pancreatic 
juice  had  the  power  of  emulsifying  fat,  but  it  was  Bernard 
who,  in  1849,  discovered  that  it  had  the  property  of  split- 
ting fats  with  the  liberation  of  fatty  acids. 

The  steapsin  of  the  pancreatic  juice  is  much  less  stable 
than  the  tryptic  and  diastatic  ferments.  It  is  very  sus- 
ceptible to  the  action  of  acids,  being  quickly  destroyed 
by  all  except  the  higher  fatty  acids.  Strong  alkalies  also 
affect  it  unfavourably.  It  is  most  active  in  a  neutral 
or  weakly  alkaline  medium,  even  0.25  per  cent,  of  sodium 
carbonate  retarding  its  activity.  Unlike  the  other  pan- 
creatic ferments,  it  is  insoluble  in  water  and  in  glycerine, 
so  that  its  effects  can  only  be  studied  by  employing  the 
fresh  gland  or  the  secretion,  but  that  it  is  an  enzyme  is 
proved  by  its  being  destroyed  on  boiling  and  by  its 
activity  being  maintained  in  the  presence  of  antiseptics. 

The  digestive  power  of  the  pancreatic  juice  for  fats  is 
considerably  increased  by  the  presence  of  bile,  and  still 
more  by  the  presence  of  bile  and  hydrochloric  acid. 
Bile  of  itself  has  little  or  no  digestive  power,  but  a  mix- 
ture of  bile  and  pancreatic  juice  can  digest  more  than 
three  times  as  much  fat  as  the  pancreatic  solution  alone. 
According  to  the  experiments  of  Wohlgemuth,  the  lipase 
of  the  pancreatic  juice  exists  partly  in  an  inactive  form, 
and  this  is  activated  by  the  accession  of  bile.  The  enzyme 
acts  best  at  the  temperature  of  the  body,  and,  although 
more  vigorous  at  higher  temperature,  up  to  a  certain 
point,  is  quickly  destroyed,  like  the  other  ferments  of  the 
secretion. 

Different  views  have  been  held  from  time  to  time  as  to 
the  exact  part  the  pancreatic  secretion  plays  in  the  diges- 
tion and  absorption  of  fat.  Although  Bernard  discov- 
ered  the   saponifying   action   of   pancreatic   juice   upon 


Physiology  119 

neutral  fats,  he  did  not  attach  much  value  to  it,  but 
described  a  "ferment  emulsif"  to  which  he  attributed 
the  chief  importance  in  the  preparation  of  fats  for  ab- 
sorption. Briicke,  however,  found  that  the  presence  of  a 
certain  amount  of  free  fatty  acid  was  sufficient  to  emul- 
sify the  remaining  neutral  fat,  and  arrived  at  the  conclu- 
sion that  the  chief  function  of  the  fat-splitting  ferment  of 
the  pancreatic  juice  was  probably  to  provide  the  fatty 
acid  for  that  purpose.  Rachford  has  shown  that  under 
favourable  conditions  a  sufficient  amount  of  fatty  acid  is 
formed  in  the  presence  of  bile  and  hydrochloric  acid  at 
room  temperature  to  form  a  spontaneous  emulsion  in 
two  minutes,  thus  explaining  Bernard's  results  without 
invoking  the  aid  of  any  special  emulsifying  ferment. 
In  consequence  of  these  and  other  observations  it  was  held 
that  only  a  small  proportion  of  the  ingested  fat  is  split 
up  into  fatty  acids  and  glycerine,  and  that  this,  aided  by 
that  naturally  present  in  most  fatty  foods,  converts  the 
remainder  into  a  fine  emulsion  which  is  absorbed  by  the 
intestinal  epithelium  and  passed  to  the  lacteals.  The 
structure  of  the  epithelial  cells  is  not,  however,  suited 
for  such  a  function,  and  fat  globules  have  not  been  ob- 
served in  their  broad  striated  border,  so  that  it  is  highly 
probable  that  the  fat  passes  through  the  walls  of  the 
cells  in  a  soluble  form  and  is  afterwards  thrown  down  in 
visible  particles.  Zawarykin's  suggestion  that  the  fat 
is  absorbed  from  the  intestine  by  lymph  cells  and  carried 
by  them  to  the  lacteals  has  been  discredited,  as  also  has 
the  theory  of  Munk  that  a  considerable  portion  of  the 
fat  is  absorbed  as  emulsified  fatty  acids.  It  is  now  gen- 
erally acknowledged  that  fat  is  absorbed  in  the  form  of 
soluble  soaps,  although  in  some  animals  a  certain  por- 
tion may  also  leave  the  intestine  as  dissolved  fatty  acids. 
The  neutral  fats  in  the  intestine  are  believed  to  be  split 
up  by  the  action  of  the  pancreatic  juice  into  fatty  acids 
and  glycerine ;  the  fatty  acids  then  unite  with  the  sodium, 


I20       The  Pancreas:  Its  Surgery  and  Pathology 

potassium,  calcium,  and  magnesium  of  the  intestinal 
juices  to  form  soluble  alkaline  soaps,  and  these  are  ab- 
sorbed, together  with  the  glycerine,  by  the  epithelial 
cells  of  the  intestinal  wall,  within  which  they  are  again 
synthesised  to  form  neutral  fat.  Miiller  has  shown  that 
the  macerated  pancreas  of  the  pig  can  split  86.4  per  cent, 
of  the  fat  of  milk  in  twenty-four  hours,  and  Rachford 
states  that  the  steapsin  of  the  pancreatic  juice  is  prob- 
ably quite  capable  of  splitting  up  all  the  fats  of  a  full 
meal  in  the  time  digestion  usually  takes  within  the  body. 
Radziejewski  has  also  proved  that  alkaline  soaps  are 
absorbed  by  the  intestine,  and  Perewoznikoff  has  dem- 
onstrated that  alkaline  soaps  and  glycerine  are  synthe- 
sised to  neutral  fats.  The  presence  of  bile  makes  the 
free  fatty  acids,  which  are  entirely  insoluble  in  water, 
soluble,  and  increases  the  solubility  of  the  alkaline  soaps. 
Its  solvent  power  is  greatly  augmented  by  the  presence 
of  lecithin,  but  is  mainly  due  to  the  bile  salts  it  contains. 

Pawlow  pointed  out  that  there  is  a  close  relationship 
between  the  amount  and  rate  of  secretion  of  the  bile  and 
pancreatic  juice,  as  he  showed  by  the  diagrams  reproduced 
in  Fig.  52.  He  also  states  that  the  amount  of  fat-split- 
ting ferment  in  the  pancreatic  secretion  is  dependent 
upon  the  quantity  of  fat  in  the  food,  basing  his  conclu- 
sion on  experiments  carried  out  by  Walther.  This 
observer  found  that  in  the  first  two  hours  after  a  meal 
of  milk,  a  juice  is  furnished  which  is  uncommonly  rich 
in  fat-splitting  ferment,  but  that  if  the  milk  is  deprived 
of  its  fat  by  filtration  the  juice  presents  a  very  low  fat- 
splitting  power,  without  any  other  alteration  in  the 
progress,  or  rate,  of  secretion;  on  again  mixing  the  fat 
with  the  milk-filtrate,  the  fat  ferment  in  the  pancreatic 
juice  is  again  increased  to  the  previous  amount. 

Recent  advances  in  our  knowledge  of  the  influences 
governing  pancreatic  secretion  make  it  doubtful  whether 
such  an  adaptation  of  the  enzymes  to  the  quality  of  the 


Physiology 


121 


food  as  Pawlow  and  others  have  described  does  occur.  In 
this  connection,  the  investigations  that  have  been  carried 
out  on  the  presence  in  the  pancreatic  secretion  of  a  fer- 
ment which  is  said  to  convert  lactose  into  galactose  and 
dextrose  are  of  interest.  Weinland,  working  at  this 
subject,  found  that  a  chloroform -water  extract  of  the 
pancreas  of  dogs  fed  on  a  diet  free  from  milk  did  not 
affect  lactose,  but  that  a  similar  extract  made  from  the 
pancreas  of  animals  which  had  been  fed  on  milk  for 
several  days  possessed  the  power  of  converting  as  much 


Fig.  52. — Curves  representing  the  hourly  secretion  of  I,  Pancreatic 
secretion;  II,  entry  of  bile  into  the  intestine:  a,  a,  After  ingestion  of 
milk;  b,  b,  after  ingestion  of  flesh;  c,  c,  after  ingestion  of  bread  (Pawlow). 

as  50  per  cent,  of  the  added  milk-sugar.  He  also  found 
that  the  pancreas  of  dogs  fed  on  meat  with  the  addition 
of  milk-sugar  contained  lactose,  but  that  the  subcuta- 
neous injection  of  lactose  for  several  days  in  succession 
had  no  effect  in  producing  the  ferment.  He  consequently 
came  to  the  conclusion  that  the  formation  of  "lactase" 
was  not  dependent  upon  any  direct  chemical  action 
exerted  by  the  lactose  or  its  products  upon  the  pancreas, 
but  that  the  adaptation  of  the  organ  to  a  milk-sugar  diet 
was  brought  about  by  a  nervous  mechanism. 


122       The  Pancreas:  Its  Surgery  and  Pathology 

After  the  discovery  of  secretin  Bainbridge  re-investi- 
gated this  question,  and  agreed  with  Weinland  that  dogs 
fed  on  biscuits  did  not  secrete  a  lactose-sphtting  ferment 
in  their  pancreatic  juice,  whereas  those  that  were  fed  on 
milk  secreted  it  in  every  instance.  Extracts  of  the  mucous 
membrane  of  milk-fed  dogs  injected  into  biscuit-fed  dogs 
were  found  by  him  to  induce  the  appearance  of  lactase 
in  the  pancreatic  secretion  of  the  latter,  so  that  the 
formation  of  the  special  ferment  by  the  pancreas  appeared 
to  depend  upon  some  substance  produced  in  the  intestinal 
wall  in  response  to  the  milk  diet.  That  this  was  not 
secretin  was  shown  by  the  negative  result  obtained  on 
injecting  secretin  prepared  from  the  duodenal  mucous 
membrane  of  milk-fed  dogs  into  biscuit-fed  dogs,  and  the 
positive  reaction  induced  by  the  injection  of  secretin 
from  the  latter  into  animals  previously  fed  on  a  milk  diet. 
He  finally  arrived  at  the  conclusion  that  the  adaptation 
of  the  pancreas  to  a  diet  containing  lactose  was  brought 
about  by  a  chemical,  and  not  a  nervous,  mechanism 
resulting  from  the  action  of  the  milk-sugar  upon  the 
intestinal  mucous  membrane,  and,  further,  that  the  reac- 
tion was  only  slowly  produced.  He  considered  that 
secretin  evokes  the  secretion  of  all  the  ferment  present 
in  the  pancreas  at  the  time  it  is  injected,  and  that  the 
composition  of  the  juice  as  regards  its  ferments  for  any 
given  meal  depended  mainly  on  the  previous  diet  of  the 
animal,  and  little,  if  at  all,  upon  the  composition  of 
the  particular  meal,  excepting  in  so  far  as  the  nature 
of  the  food  determined  the  amount  of  hydrochloric  acid 
secreted  by  the  stomach. 

These  conclusions  with  regard  to  the  adaptation  of  the 
pancreas  to  the  presence  of  lactose  in  the  food  have  been 
adversely  criticised  by  Bierry  and  Plimmer,  who  attribute 
the  results  obtained  to  faulty  methods.  Their  criticism 
appears  to  be  well  founded  and  is  supported  by  a  consid- 
erable amount  of  careful  experimental  work.     They  agree 


Physiology  123 

with  PopeHski  that  the  composition  and  amount  of  the 
pancreatic  secretion  are  determined  solely  by  the  inten- 
sity and  duration  of  the  stimulus.  Plimmer  also  points 
out  that  the  work  of  Vasilieff  and  Walther,  on  which 
Pawlow  based  his  inferences  concerning  the  lipase  and 
trypsin,  was  carried  out  before  the  discovery  of  entero- 
kinase,  so  that  its  value  is  seriously  diminished.  It  may 
therefore  be  concluded  that,  at  present,  there  is  no  evi- 
dence of  any  adaptation  of  the  pancreatic  secretion  of  the 
diet,  the  only  factor  that  influences  it  probably  being  the 
amount  of  secretin  formed  and  the  duration  of  its  flow 
into  the  blood. 

The  milk-curdling  ferment  of  the  pancreatic  juice  is 
probably  not  of  much  physiological  importance.  In  its 
general  action  it  resembles  renin,  but  the  results  produced 
by  the  two  ferments  are  not  exactly  alike.  Kiihne  was 
the  first  to  demonstrate  that  an  extract  made  from  the 
pancreas  of  the  dog  produced  clotting  in  milk,  but  Gamgee 
pointed  out  that  this  does  not  prove  that  the  secretion  of 
the  organ  possesses  the  same  property.  Halliburton  and 
Brodie  found,  however,  that  pancreatic  juice  does  pro- 
duce a  change  in  the  caseinogen  of  milk,  although  the 
action  differs  from  that  of  rennet  in  some  particulars. 
They  showed  that  the  addition  of  pancreatic  juice  to 
milk  at  a  temperature  of  35°  to  40°  C.  caused  a  finely 
granular  precipitate  of  casein  to  form,  but  that  the  milk 
still  remained  fluid.  On  being  cooled,  however,  it  formed 
a  coherent  curd,  which  again  broke  up  into  fine  granules 
when  the  temperature  was  raised.  By  the  action  of 
rennet  this  "pancreatic  casein"  can  be  transformed  into 
true  casein.  Wohlgemuth,  experimenting  with  the  secre- 
tion from  a  pancreatic  fistula,  states  that  the  rennetic 
ferment  is  mainly  present  in  the  form  of  a  pro-ferment 
which  is  actuated  by  the  intestinal  juice  and  hydrochloric 
acid. 

From  being  considered  as  merely  an  organ  accessory 


124       The  Pancreas:  Its  Surgery  and  Pathology 

to  the  digestive  tract,  the  pancreas  has  come,  in  recent 
years,  to  be  regarded  as  having  a  most  important  influence 
upon  the  metabohsm  of  the  body.  Not  only  may  disease 
of  the  pancreas  lead  to  wasting  from  imperfect  digestion 
and  absorption  of  food,  but,  in  certain  cases,  it  gives  rise 
to  glycosuria  and  other  symptoms  of  diabetes,  which 
suggest  that  it  is  of  fundamental  importance  in  the 
assimilation  of  carbohydrate  materials  by  the  tissues  of 
the  body.  The  mechanism  of  this  influence  is  as  yet  a 
matter  for  surmise,  but  it  is  now  generally  assumed  that, 
in  addition  to  its  external  secretion  of  digestive  ferments 
into  the  alimentary  canal,  the  pancreas  forms  an  internal 
secretion  through  which  it  controls  carbohydrate  meta- 
bolism. The  elaboration  of  this  internal  secretion  has 
been  attributed  by  some  to  the  islands  of  Langerhans, 
but  as  the  discussion  of  this  subject  is  intimately  bound 
up  with  the  relationship  of  the  pancreas  to  diabetes,  it 
will  be  considered  later,  under  that  heading. 

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Physiology  125 

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Pawlow:    "The  Work  of  the  Digestive  Glands,"  tr.  W.  H.  Thompson, 

1902. 
Perowoznikoff:   Centralbl.  f.  d.  med.  Wissensch.,  1876,  S.  851. 
Plirnmer:   Journ.  of  Physiol.,  xxxiv,  1906. 
Popielski:   Gazette  clinique  de  Botkin,  1900. 
Rachford:   Journ.  of  Physiol.,  1891,  xii,  72. 
Schafer:    "Text-book  of  Physiology,"  i. 
Schrnidt:  Maly,  Hermann's  "Handbuch, "  v  (2),  189. 
Starling:    "Recent  Advances  in  the  Physiology  of  Digestion,"  1906. 
Vernon:   Journ.  of  Physiol.,  xxvii,  288;    Ibid.,  xxviii,  378. 
Weinland:  Zeitschr.  f.  Biologic,  1899,  xxxviii,  607;   Ibid.,  1900,  xl,  386. 
Wertheimer  and  Lepage:   Journ.  de  Physiologic,  lii,  365. 
Wohlgemuth:    Biochem.  Zeit.,  1906,  ii,  264. 
Zawadsky:   Centralbl  f.  Physiol.,  v,  179. 
Zawarykin:   Arch.  f.  d.  gen.  Physiol.,  Bonn,  1883,  xxxi,  231. 


CHAPTER  VIII 
PATHOLOGY 

Our  present  knowledge  of  the  nature  and  etiology  of 
the  diseases  to  which  the  pancreas  is  liable  has  resulted 
•mainly  from  clinical  observation  and  experimental  re- 
search upon  the  lower  animals.  Relying  upon  the  naked- 
eye  appearance  of  the  organ  as  seen  on  the  post-mortem 
table,  it  has  been  assumed,  until  recently,  that  pancreatic 
lesions  were  among  the  curiosities  of  medicine,  and  were 
therefore  of  little  or  no  practical  importance.  Since 
1889,  when  Pitz  published  his  work  upon  acute  pancreati- 
tis and  von  Mering  and  Minkowski  first  brought  forward 
the  results  of  their  investigations  upon  the  relation  of  the 
pancreas  to  diabetes,  it  has  been  slowly  recognised, 
however,  that  diseases  of  the  pancreas  are  far  from  being 
uncommon,  and  that  disturbances  of  its  functions,  besides 
interfering  with  the  normal  processes  of  digestion,  may  be 
responsible  for  signs  and  symptoms  which  had  hitherto 
been  unexplained  or  were  usually  referred  to  other 
causes. 

Hale  White,  searching  the  post-mortem  records  of 
Guy's  Hospital  for  fourteen  years,  1884  to  1897  inclusive, 
found  that  in  the  6708  post-mortems  performed  during 
that  period  the  pancreas  had  been  regarded  by  the  mor- 
bid anatomists  in  charge  as  diseased  or  injured  in  142 
instances;  that  is,  in  2  per  cent,  of  all  cases  dying  in  a 
large  general  hospital.  In  55  there  was  primary  or  sec- 
ondary malignant  disease  of  the  pancreas;  a  cirrhotic 
hard  or  small  atrophied  gland  was  found  in  45,  and  there 
were  noticeable  fatty  changes  in  9.  Three  of  the  remain- 
ing T,T,  were  instances  of  hemorrhage  into  the  pancreas, 

126 


Pathology  127 

3  were  cases  of  pancreatic  calculi,  2  were  examples  of 
pancreatic  cysts,  i  was  a  hydatid  cyst  of  the  pancreas,  in 
3  there  was  suppuration  of  the  gland,  and  4  showed 
evidence  of  tuberculosis,  while  the  balance  was  made  up 
of  a  miscellaneous  collection  of  more  or  less  rare  diseases 
and  injuries  presenting  obvious  lesions.  Recent  statis- 
tics based  upon  microscopical  investigations  have  shown 
that  in  many  instances  the  gross  appearance  of  thp  organ 
is  unchanged  in  the  presence  of  considerable  alterations 
in  its  minute  anatomy,  and  that  acute  and  chronic  in- 
flammations may  bring  about  only  slight  and  easily 
overlooked  microscopical  changes.  Bosanquet  found  on 
examining  sections  of  the  pancreas  from  170  cases  dying 
in  hospital  from  a  variety  of  diseases,  and  ranging  in 
age  from  four  days  to  over  ninety  years,  that  a  certain 
amount  of  fibrosis  was  present  in  13  per  cent. ;  allowing, 
as  he  suggests,  that  some  increase  of  fibrous  tissue  is  the 
usual  accompaniment  of  old  age  and  that  10  per  cent,  of 
his  cases,  who  were  over  forty  years  of  age,  may  be 
excluded  on  that  score,  there  still  remained  5  per  cent, 
under  that  age  in  which  the  microscope  revealed  a  fibrosis, 
probably  of  pathological  origin,  as  compared  with  the 
0.7  per  cent,  recognised  by  the  morbid  anatomists  at 
Guy's  Hospital  as  showing  evidence  of  chronic  inflamma- 
tory changes.  It  is  evident,  therefore,  that  post-mortem 
records  cannot  be  relied  upon  either  for  precise  informa- 
tion as  to  the  relative  frequency  of  diseases  of  the  pancreas 
or  for  data  on  which  to  base  an  accurate  estimate  of  the 
true  importance  of  the  various  morbid  conditions  to  which 
it  is  liable,  unless  the  results  of  naked-eye  observations 
have  been  checked  by  microscopical  examinations,  and, 
since  this  is  so  rarely  done  even  at  the  present  time,  there 
is  not  a  sufficient  mass  of  systematic  observations  to 
allow  of  any  satisfactory  conclusions  being  reached  upon 
these  points,  apart  from  clinical  evidence. 

The  difficulties  met  with  in  the  recognition  of  morbid 


128       The  Pancreas:  Its  Surgery  and  Pathology 

conditions  of  the  pancreas  in  the  post-mortem  room  are  in 
part  due  to  the  rapid  changes  that  take  place  in  the  organ 
at  and  after  death,  and  to  the  appearance  and  colour  of 
the  gland  as  seen  at  autopsy.  Apart  from  the  putre- 
factive changes  which  rapidly  supervene  under  suitable 
conditions,  the  pancreas  is  said  by  Chiari  to  be  more  or 
less  altered  by  a  process  of  auto-digestion  that  sets  in 
immediately  before,  or  shortly  after,  death  in  some  50 
per  cent,  of  cases.  In  this  condition  the  organ  is  white 
and  flaccid  and,  under  the  microscope,  is  found  to  stain 
uniformly  with  acid  dyes.  These  difficulties  are  to  a 
large  extent  obviated  in  experimental  researches  upon 
animals  and  in  observations  made  on  man  in  the  course 
of  abdominal  operations.  Experiments  upon  animals  can 
be  conducted  under  the  most  favourable  circumstances, 
and  give  at  least  some  indication  of  what  may  be  expected 
in  the  human  subject  under  similar  conditions,  while  the 
surgeon  has  the  advantage  over  the  pathologist  that  he 
can  examine  and  handle  a  living  organ  unaffected  by 
self -digestion  and  post-mortem  changes,  although  his 
investigations  must  naturally  suffer  from  not  being  as 
searching  and  conclusive  as  the  pathologist  is  able  to 
carry  out.  Only  those  who  have  seen  and  handled  an 
inflamed  pancreas  can  realise  how  an  engorgement  and 
swelling  of  the  gland  which  was  perfectly  evident  at  the 
time  of  operation  may,  if  the  organ  is  examined  a  few 
hours  later,  on  the  post-mortem  table,  have  entirely 
disappeared,  leaving  a  structure  that  is  pale  and  flaccid, 
presenting,  in  fact,  no  marked  deviation  from  the  normal. 
The  pathological  conditions  met  with  in  the  pancreas 
resemble  in  many  respects  those  encountered  in  the  liver, 
and  in  some  instances  a  similar  morbid  state  is  found  in 
both  organs.  Their  parenchyma  is  liable  to  be  affected 
by  the  same  degenerative  changes,  and  chronic  inflamma- 
tion in  the  one  gives  rise  to  results  very  similar  to  those 
induced  in  the  other.     The  ducts  of  both  organs  are  not 


Pathology  129 

uncommonly  involved  in  the  same  pathological  processes, 
and  the  morbid  influences  reaching  the  one  are  also  liable 
to  affect  the  other.  There  are,  however,  certain  affections 
of  the  pancreas  to  which  no  strictly  analogous  condition 
can  be  found  in  the  liver,  and  it  is  to  these  that  attention 
has  been  largely  devoted  in  most  text-Vjooks  of  medicine 
and  pathology.  In  view,  however,  of  the  important  part 
that  the  pancreas  takes  in  the  processes  of  digestion  and 
internal  metabolism,  the  neglected  lesions,  that  are  often 
masked  by  the  more  obvious  and  striking  affections  of 
other  organs,  are  no  less  worthy  of  attention,  for,  although 
at  first  sight  the  pancreas  may  appear  to  play  but  a 
subsidiary  part  in  the  production  of  the  symptoms  met 
with  in  some  of  these  conditions,  it  becomes  increasingly 
plain,  as  our  methods  of  investigation  are  improved,  that 
the  pancreatic  lesions  are  responsible  for  much  that  has 
hitherto  been  attributed  to  disease  of  other  organs,  or 
been  altogether  unexplained. 

Atrophy. — In  common  with  other  organs  of  the  body, 
the  pancreas  is  liable  to  diminish  in  size  and  weight  with 
advancing  years,  and  as  the  result  of  chronic  diseases 
and  marasmus  its  bulk  may  be  reduced  considerably 
below  the  normal  standard.  Senile  atrophy  of  the  gland 
is  found,  in  many  instances,  to  be  accompanied  by  sclerotic 
changes  in  the  vessels  supplying  it  with  blood,  while  in 
others  it  is  no  doubt  the  consequence  of  general  malnutri- 
tion, such  as  also  gives  rise  to  the  condition  in  chronic 
wasting  diseases.  Atrophy  of  the  pancreas  is  met  with 
in  a  considerable  number  of  cases  of  diabetes.  According 
to  Hansemann,  diabetic  and  cachectic  atrophy  can  be 
distinguished  both  macroscopically  and  microscopically, 
and  while  the  former  always  gives  rise  to  diabetes,  the 
latter  only  does  so  in  advanced  cases. 

The  pancreas  in  diabetic  atrophy  is  said  to  be  usually 
flabby  and  somewhat  dark  in  colour.  Its  bulk  is  espe- 
cially diminished  in  a  transverse  diameter,  so  that  it 
9 


130       The  Pancreas:  Its  Surgery  and  Pathology 


assumes  a  fiat  shape.  The  lobules  are  small,  and  the  sur- 
rounding connective  tissue  and  fat  extend  into  the  organ 
so  that  it  is  often  only  removed  with  difficulty.  At  times 
large  adhesions  and  new-formed  bands  connect  the  pan- 
creas with  surrounding  structures.  Microscopically  the 
secreting  cells  show  no  particular  change,  apart  from  the 
atrophy ;  there  is  no  marked  opacity,  fatty  degeneration, 
or  pigmentation.      The  stroma  is  scanty,  but  the  gaps 

caused  by  the  diminution  in  size 
of  the  gland  lobules  are  more  or 
less  obliterated.  Although  the 
organ  is  largely  fibrous,  there 
are  here  and  there  patches  of 
recent  cellular  infiltration,  giv- 
ing rise  to  a  condition  resem- 
bling that  met  with  in  certain 
forms  of  granular  atrophy  of  the 
kidney. 

In  cachectic  atrophy,  on  the 
other  hand,  the  adjacent  fat 
tissue  has  disappeared  to  a  de- 
gree corresponding  to  the  gen- 
eral emaciation,  and  the  gland 
is  sharply  defined  from  the  sur- 
rounding structures.  In  shape  it 
is  cylindrical,  its  thickness  and 
its  height  being  about  equal.  It 
is  not  flabby,  but  of  a  firm  or  moderate  consistency. 
Under  the  microscope  both  the  lobules  and  the  individual 
cells  are  small,  the  stroma  is  atrophied  and  scanty,  and 
the  cells  are  not  especially  pigmented. 

Although  these  observations  of  Hansemann's  summarise 
the  points  by  which  cachectic  atrophy  may  be  distin- 
guished from  other  conditions  in  which  diabetes  is  accom- 
panied by  changes  in  the  size  of  the  gland,  it  has  not  been 
shown  that  his  "diabetic  atrophy"  is  a  pathological  entity, 


Fig-  53-— Atrophy  of 
the  pancreas  (Univ.  Coll. 
Hosp.  Museum,  3194  A). 


Pathology  131 

or  that  the  condition  he  describes  under  that  name  is  in- 
variably accompanied  by  diabetes;  in  fact,  it  is  probable, 
as  we  shall  show  later,  that  there  is  no  special  form  of  dia- 
betic atrophy,  but  that  atrophy  of  the  pancreas  arising  from 
a  variety  of  causes  may  be  accompanied  by  glycosuria. 
One  of  the  commonest  causes  both  of  pancreatic  atrophy 
and  of  diabetes  is  chronic  interstitial  pancreas,  and  it  is 
to  this  probably  that  the  so-called  atrophy  of  diabetes, 
described  by  Hansemann,  is  in  most  instances  due. 

Williamson,  Opie,  and  others  have  described  cases  of 
diabetes  in  which  the  pancreas  was  diminished  n  size 
to  an  extent  bearing  no  relation  to  the  wasting  of  other 
organs,  although  no  changes  could  be  observed  in  the 
structure  of  the  gland.  Opie  suggests  that  in  these 
instances  the  condition  is  possibly  congenital,  and  that, 
since  the  pancreas  is  unusually  small,  it  fails  to  meet  the 
demands  upon  it  at  some  period  of  life,  so  that  diabetes 
results.  He  considers  that  when  the  weight  of  the  pan- 
creas falls  below  65  grams  (2  ounces)  it  is  abnormal. 

A  condition  apparently  due  to  congenital  deficiency 
of  the  pancreatic  functions  has  been  described  by  Byrom 
Bramwell  under  the  name  of  "pancreatic  infantilism." 
The  patient  in  whom  this  diagnosis  was  made  was  a  youth 
of  nineteen  whose  bodily  development  had  apparently 
been  arrested  about  the  age  of  eleven  years.  He  was 
bright  and  intelligent,  perfectly  formed,  and  presented 
none  of  the  physical  alterations  suggestive  of  sporadic 
cretinism.  The  abdomen  was  swollen  and  tympanitic, 
and  for  nine  years  before  he  came  under  observation  he 
had  suffered  from  chronic  diarrhoea.  The  urine  was  free 
from  sugar.  From  careful  investigations  of  the  urine 
and  fceces  it  was  concluded  that  the  pancreatic  secretion 
was  defective  or  completely  absent.  That  this  was  the 
case  was  proved  by  the  remarkable  improvement  brought 
about  by  the  administration  of  a  glycerine  extract  of 
pancreas,  for  as  the  result  of  this  treatment  the  stools 


132       The  Pancreas:  Its  Surgery  and  Pathology 


were  reduced  from  five  or  six  loose  motions  a  day  to  two, 
one  of  which  was  formed;  in  two  years  he  grew  five 
inches,  and  increased  i  stone  8  pounds  in  weight,  although 
for  the  previous  eight  years  he  was  said  not  to  have  grown 
at  all;  the  sexual  development,  which  before  treatment 
was  begun  was  infantile,  progressed  in  a  normal  manner; 

the  patient  looked 
much  older,  and 
his  voice,  which 
had  previously 
been  high-pitched 
and  childish,  be- 
came of  low  tone 
and  rough. 

Thomson  has 
since  described 
two  apparently 
similar  cases  in 
males  and  Ren- 
toul  has  recorded 
the  case  of  a  fe- 
male with  similar 
symptoms.  The 
first  of  Thom- 
son's cases  was  a 
man  of  twenty- 
four  who  was 
about  the  size  of 
a  boy  of  ten ;  the 
second  was  a  boy 
of  eighteen  who  resembled  a  child  of  eight  or  nine  years 
in  size  and  development;  both  suffered  from  chronic  in- 
tractable diarrhoea.  In  Rentoul's  case  the  patient  was 
a  girl  of  eighteen  whose  parents  complained  that  for 
seven  years  she  had  not  grown,  and  that  she  had  been 
troubled  all  her  life  with   diarrhoea.     This   patient  was 


Fig.  54. — Pancreatic  infantilism;  a,  Be- 
fore treatment;  b,  after  treatment  (Byrom 
Bramwell). 


Pathology 


133 


also  much  benefited  by  pancreatic  extract,  putting  on 
9^  pounds  in  weight  and  adding  almost  2  inches  to  her 
height  in  a  little  over  four  months,  besides  developing 
sexually  and  improving  in  her  general  condition. 

Whether  pancreatic  infantilism  is  due  to  congenital 
atrophy  of  the  pancreas  or,  as  has  been  suggested,  to 
general  fibrosis  from  congenital  syphilis,  it  would  appear 
that  while  in  patients  who  present  such  symptoms  the 
pancreas  is  sufficient  for  the 
metabolic  needs  of  the  body 
for  the  first  eight  or  nine  years 
of  life,  it  is  subsequently  un- 
able to  keep  pace  with  the 
calls  upon  it,  so  that  the  gen- 
eral nutrition  and  development 
suffer  in  consequence.  It  is 
worthy  of  note,  however,  that 
the  deficiency  appears  to  be 
confined  to  the  •  digestive  func- 
tions of  the  gland  and  does 
not  interfere  with  carbohydrate 
metabolism,  for  none  of  the  re- 
corded cases  have  had  glyco- 
suria. Whether  diabetes  will 
subsequently  develop  or  not  it 
is  as  yet  too  early  to  say,  but 
the  history  of  a  case  in  this  connection  would  be  well 
worth  following  up  as  growth  advanced. 

As  the  result  of  pressure  exerted  from  without  by 
aneurysms,  new-growths,  etc.,  the  pancreas  may  undergo 
secondary  atrophic  changes,  and  similar  consequences 
may  also  follow  the  chronic  interstitial  inflammation 
accompanying  pancreatic  calculi,  pancreatic  cysts,  hsemor- 
rhage,  or  abscess  formation.  In  some  instances  the 
changes  may  be  so  great  that  the  gland  tissue  almost 


Fig-  55- — Fibrosis  of 
the  pancreas  (St.  George's 
Hospital  Museum). 


134      The  Pancreas:  Its  Surgery  and  Pathology 

entirely  disappears  and  the  organ  is  only  represented  by 
a  small  mass  of  fibrous  tissue. 

Fatty  Infiltration  and  Degeneration. — The  interstitial 
connective  tissue  of  the  pancreas  normally  contains  a 
certain  amount  of  fat,  and  this  is  liable  to  increase 
under  pathological  conditions.  The  increase  that  takes 
place  in  simple  cachectic  atrophy  has  already  been  re- 


Fig.  56. — Chronic  atrophic  pancreatitis.     Island  of  Langerhans,  sur- 
rounded by  fat,  instead  of  acini  (Deaver  and  Miiller). 

ferred  to.  In  general  obesity,  especially  when  con- 
nected with  alcoholism,  a  similar  overgrowth  of  fat  is 
frequently  encountered.  This  condition  is  often  com- 
bined with  fatty  degeneration,  and,  in  extreme  cases, 
may  result  in  the  whole  organ  being  transformed  into  a 
mass  of  fatty  tissue.  It  is  then  of  a  yellow  or  yellowish- 
white  appearance,  soft,  and  somewhat  larger  than  normal. 


Pathology  135 

On  section  it  is  found  to  be  lobulated  and  to  consist  of 
masses  of  fat  separated  by  more  or  less  well-marked 
strands  of  fibrous  tissue  in  which  the  remains  of  the 
larger  ducts,  and  perhaps  some  remnants  of  the  gland 
structures,  are  embedded.  Fatty  degeneration  is  caused 
most  frequently  by  inflammation  of  the  gland,  but  it 
also  occurs  in  infectious  diseases  and  toxaemias,  and  may 
result  from  poisoning  by  phosphorus  or  mineral  salts. 
Extreme  degrees  of  fatty  change  are  frequently  found 
associated  with  pancreatic  lithiasis.  Fatty  degeneration 
of  the  parenchyma  is  preceded  in  the  first  instance  by 
cloudy  swelling,  the  cells  microscopically  being  found 
to  be  somewhat  enlarged,  opaque,  and  very  granular. 
To  the  naked-eye  the  gland  is  hypersemic  and  enlarged. 
At  first  it  is  hard  to  the  touch,  but,  as  the  degenerative 
process  advances,  becomes  softer  and  of  a  white  or 
yellowish-white  colour.  Under  the  microscope  the  epithe- 
lium is  then  found  to  contain  numerous  fat  globules  and 
the  interstitial  tissue  to  be  oedematous. 

Amyloid  degeneration  of  the  pancreas  occurs  under  the 
same  conditions  as  in  other  organs,  and  is  associated  with 
a  similar  lesion  in  other  tissues  of  the  body.  It  primarily 
affects  the  small  blood-vessels,  but  may  eventually 
involve  the  larger  vessels  and  the  membrana  propria  of 
the  acini.  The  gland  cells  undergo  fatty  degeneration 
and,  in  part,  disintegrate.  Hennigs  found,  in  one  hun- 
dred and  fifty-five  cases  of  general  amyloid  disease,  six 
in  which  the  pancreas  was  affected.  Rokitansky  states 
that  sometimes  the  degenerative  changes  are  limited  to 
the  pancreas  and  may  affect  the  secreting  epithelium, 
but  this  is  denied  by  Friedrich  and  Kyber.  Opie  suggests 
that  the  condition  observed  by  Rokitansky  in  these  cases 
was  in  reality  hyaline  degeneration. 

Hyaline  degeneration  of  the  parenchyma  of  the  pancreas 
has  been  described  by  Saunby  in  a  case  of  diabetes,  and 
Opie  has  also  published  an  account  of  a  diabetic  whose  pan- 


136       The  Pancreas:  Its  Surgery  and  Pathology 

areas  showed  patches  of  hyaHne  degeneration,  apparently 
replacing  the  islands  of  Langerhans,  but  also  affecting  the 
secreting  parenchyma.  Other  cases  of  hyaline  degenera- 
tion have  since  been  recorded  by  a  number  of  investigators. 
All  have  been  associated  with  diabetes  and  the  degenera- 
tive changes  have  been  said  to  have  been  limited  to  the 
islands  of  Langerhans.     According  to  Opie,  hyaline  de- 


§    I 

/   % 

'       r 

J* 


:r 


««.© 


"«©! 


rv 


V  Ac#%.%*^#l.  ,/ 


\wi^  -^-\/-^  T..'/'?' 

Fig.  57. — Hyaline  degeneration  of  the  pancreas  (Opie). 


generation  first  manifests  itself  by  an  increase  in  the  size 
of  the  cells  of  the  islets  and  an  alteration  of  their  pro- 
toplasm. With  the  death  of  the  cells  their  nuclei  disap- 
pear, and  the  cell  protoplasm,  which  stains  with  acid 
dyes,  remains  for  a  time  granular,  but  subsequently 
becomes  homogeneous.  The  small  masses  of  hyaline 
material  then  fuse  with  one  another  and  form  large  collec- 
tions which  lie  in  contact  with  the  fibrous  septa  of  the 


Pathology  137 

island.  After  complete  transformation  of  its  cells  the 
island  is  found  to  be  represented  by  a  hyaline  mass, 
penetrated  by  the  remains  of  altered  capillaries.  In 
some  instances  the  degenerative  process  may  spread  to 
the  secreting  parenchyma,  but,  as  a  rule,  it  is  limited  to 
the  cell  islets.  The  hyaline  material  stains  with  eosin, 
picric  acid,  and  other  acid  dyes,  but  shows  no  affinity 
for  nuclear  stains;  on  treatment  with  iodine,  gentian- 
violet,  methyl-violet,  or  iodine-green  it  does  not  give  the 
amyloid  reactions,  and  it  resists  the  action  of  strong  acids 
and  alkalies.  Unlike  amyloid  changes,  hyaline  degenera- 
tion of  the  pancreas  is  limited  to  that  organ,  for  the  blood- 
vessels of  the  liver,  'spleen,  and  kidneys  appear  to  be 
unaffected.  Its  etiology  is  uncertain,  but  the  fact  that, 
in  most  cases,  there  has  also  been  chronic  interstitial 
pancreatitis  of  the  interacinar  type  has  suggested  that  it 
may  possibly  be  due  to  interference  with  the  circulation 
in  the  cell  islets.  Opie,  however,  is  of  opinion  that  both 
lesions  are  due  to  some  irritant  carried  to  the  pancreas 
by  the  blood. 

Focal  Necrosis. — In  the  body  of  a  male  negro,  who  had 
suffered  from  diabetes,  Opie  met  w4th  a  condition  of  the 
pancreas  resembling  the  focal  coagulation  necrosis  fre- 
quently observed  in  the  liver  in  typhoid  fever  and  other 
infections.  To  the  naked  eye  the  organ  presented  no 
notable  abnormality,  but  microscopically  there  was  some 
increase  of  the  connective  tissue,  and  foci  of  necrosis,  in- 
volving a  considerable  number  of  acini,  were  found  in  the 
parenchyma.  In  some  places  the  islands  of  Langerhans 
were  found  to  be  implicated  in  the  process,  and,  rarely, 
the  cells  of  an  island  had  undergone  necrosis  while  the 
surrounding  acini  were  normal.  The  affected  cells  pre- 
served their  identity  and  were  not  fused  into  homoge- 
neous masses,  as  in  hyaline  degeneration,  but  they  had 
lost  their  nuclei  and  stained  deeply  with  eosin. 

Local  hcEfnorrhages  into  the  tissues  of  the  pancreas  are 


138       The  Pancreas:  Its  Surgery  and  Pathology 

relatively  frequent.  In  some  instances  they  are  asso- 
ciated with  extravasations  of  blood  in  other  organs  and 
result  from  circulatory  disturbances,  due  to  diseases  of 
the  heart,  lungs,  and  liver,  or  from  altered  conditions 
of  the  blood,  such  as  occur  in  infectious  diseases,  purpura, 
scurvy,  phosphorus-poisoning,  etc.  Diseases  of  the  blood- 
vessels, such  as  atheroma,  and  fatty  degeneration,  or 
alcoholic  or  syphilitic  arteritis,  may  also  be  associated 
with  haemorrhage  into  the  gland.  Among  other  causes 
of  pancreatic  haemorrhage  may  be  mentioned  fatty 
degeneration  of  the  gland  cells,  with  a  deposit  of  fat  in 
the  pancreas,  the  result  of  alcoholism  or  of  general  obesity, 
fat  necrosis  in  the  gland  or  its  vicinity,  disintegration  of 
neoplasms,  embolism  of  a  pancreatic  artery,  and  inflam- 
mations of  the  gland,  which  last  will  be  considered  in 
detail  subsequently.  Although  the  pancreas  lies  in  a 
sheltered  position  within  the  abdominal  cavity,  its 
tissues  are  comparatively  soft  and  easily  bruised,  so  that 
even  slight  injury  takes  more  effect  upon  it  than  upon 
firmer  organs,  and  may  give  rise  to  an  effusion  of  blood. 
This  susceptibility  of  the  pancreas  to  injury  is  shown  by 
the  effects  of  manipulations  of  the  gland  in  animals, 
and  must  be  borne  in  mind  in  conducting  operations  for 
gall-stones  in  the  common  duct,  for  it  is  then  often 
necessary  to  manipulate  the  head  of  the  pancreas  rather 
freely.  Large  pancreatic  haemorrhages  are  of  great 
clinical  interest  and  are  probably  more  common  than  is 
usually  thought.  They  may  occur  in  the  substance  of 
the  gland  and  disintegrate  it,  or  on  the  surface  and  lead 
to  extensive  effusion,  either  beneath  the  peritoneum  or 
into  the  lesser  sac. 

Besides  the  local  hemorrhages  not  associated  with 
inflammatory  change,  which  may  be  termed  "pancreatic 
apoplexy,"  and  the  form  accompanying  acute  inflamma- 
tion, known  as  "hemorrhagic  pancreatitis,"  there  is,  in 
many  pancreatic  affections,  a  tendency  to"  general  haemor- 


Pathology 


139 


rhage  from  wounds  or  mucous  surfaces,  and  to  petechial 
haemorrhage  into  the  skin,  or  to  more  extensive  bleeding 
into  the  subcutaneous  tissue.  It  is  well  recognized  that 
a  hasmorrhagic  tendency  coexists  with  cancer  of  the  head 
of  the  pancreas,  and  it  is  generally  thought  to  be  alto- 


Fig.  58. — Haemorrhage  into  the  pancreas  produced  by  the  injection 
of  zinc  chloride,  showing  how  the  blood  infiltrates  and  breaks  up  the 
gland  tissue:  a,  Blood-vessel  distended  with  blood;  b,  extra vasated 
blood  in  the  parenchyma  between  the  lobules;  c,  normal  pancreatic 
tissue  (Oser). 


gether  dependent  upon  the  attendant  cholasmia.  There 
is,  however,  much  less  danger  from  haemorrhage  in  patients 
jaundiced  from  gall-stones  than  in  those  in  whom  the 
jaundice  depends  upon  disease  of  the  pancreas.  The 
haemorrhagic  tendency  is,  moreover,  also  present,  although 
perhaps  not  to  quite  the  same  extent,  in  some  pancreatic 
affections  not  associated  with  cholasmia.     Investigations 


I40       The  Pancreas:  Its  Surgery  and  Pathology 

of  the  blood  that  we  have  carried  out  in  a  number 
of  cases  of  cancer  of  the  head  of  the  pancreas  and  in 
inflammatory  affections  of  the  gland,  with  and  without 
jaundice,  have  shown  that  the  coagulation  time  of  the 
blood,  as  estimated  by  Wright's  method,  is  considerably 
delayed  and  the  number  of  blood  platelets  markedly 
diminished.  It  is  well  known  that  a  diminution  in  the 
lime  salts  of  the  blood  interferes  with  its  power  of  coagu- 
lating, and  that  the  prolonged  coagulation  time  and 
tendency  to  haemorrhage  in  pancreatitis  are  probably  due 
to  a  great  extent  to  this  cause  is  suggested  by  the  benefi- 
cial effects  resulting  from  the  administration  of  calcium 
chloride.  Further  evidence,  pointing  in  the  same  direc- 
tion, is  also  afforded  by  the  composition  of  pancreatic 
calculi,  which  are  peculiarly  rich  in  calcium,  and  by  the 
very  frequent  presence  of  a  large  deposit  of  calcium  oxa- 
late crystals  in  the  urine  in  cases  of  pancreatitis. 

Inflammatory  Affections. — Judging  from  post-mortem 
records,  inflammatory  affections  of  the  pancreas  must  be 
considered  as  amongst  the  rarest  of  diseases,  but  recent 
clinical  observations  and  operative  experience  have  shown 
that  such  a  conclusion  would  be  far  from  being  the  truth. 
As  far  back  as  1672,  Tulpius  described  a  diffuse  pancreatic 
abscess  of  pyaemic  origin,  and  Matthew  Baillie,  in  a  work 
on  "Morbid  Anatomy,"  figured  what  he  called  a  hard 
pancreas,  with  the  lobules  distinct,  but  which  would  now 
be  considered  as  an  example  of  chronic  pancreatitis.  In 
the  same  work  Baillie  also  gives  a  drawing  of  a  pancreas 
in  which  concretions  were  discovered  in  the  ducts  post- 
mortem, and  which  shows  the  changes  that  accompany 
them,  as  well  as  the  relations  of  the  bile  and  pancreatic 
ducts,  in  a  striking  manner.  Portal  in  1804  described  a 
case  of  acute  suppurative  pancreatitis,  following  an  attack 
of  gout  in  the  feet,  and  Percival  in  1818  recorded  a  well- 
marked  case  of  pancreatic  abscess  associated  with  jaun- 
dice. 


Pathology 


141 


Acute  pancreatitis  with  fat  necrosis  was  first  described 
by  Balser  in  1879,  but  it  was  not  until  1889,  when  Fitz 
published  his  classical  papers,  that  the  attention  of  the 
medical  world  was  really  aroused  and  inflammatory  dis- 
eases of  the  pancreas  came  to  be  carefully  studied  at  the 
bedside  and  in  the  laboratory.  Much  experimental  work 
has  been  since  devoted  to  the  investigation  of  acute  pan- 
creatitis, for  opportunities 
of  studying  the  disease 
clinically,  although  more 
frequent  than  has  been 
supposed,  are  still  not 
common.  Our  present 
knowledge  of  the  chronic 
inflammatory  affections  of 
the  pancreas,  however, 
while  dependent  to  a  cer- 
tain extent  upon  the  re- 
sults of  experiment  per- 
formed in  animals,  is 
mainly  due  to  clinical  re- 
search and  observations 
made,  in  the  course  of  op- 
erations upon  the  biliary 
tract. 

Experiment  has  shown 
that  the  injection  of  a 
variety  of  substances  into 

the  pancreas,  either  directly  into  the  parenchyma  or 
through  the  duct  of  Wirsung,  gives  rise  to  severe,  and 
often  rapidly  fatal,  inflammation,  the  severity  of  the 
lesion  depending  upon  the  nature  and  amount  of  the 
substance  injected. 

The  most  varied  and  successful  experiments  have  been 
carried  out  by  Flexner,  who  found  that  dilute  hydrochloric, 
nitric,   sulphuric,   or  chromic   acid,   solutions  of  caustic 


Fig.  59. — Acute 
pancreatitis  (Univ 
Museum,  3194  B). 


hemorrhagic 
Coll.      Hosp. 


142       The  Pancreas:  Its  Surgery  and  Pathology 

alkalies,  formalin,  or  suspensions  of  bacillus  pyocyaneus 
or  of  bacillus  diphtheriae,  when  injected  into  the  pancre- 
atic duct  of  dogs  gave  rise  to  acute  inflammation  of  the 
gland,  which,  in  rapidly  fatal  cases,  was  commonly  accom- 
panied by  hsemorrhage,  fat  necrosis,  and  glycosuria. 
In  those  instances  in  which  the  animal  survived  for  some 
time  necrosis  of  portions  of  the  gland,  abscess  formation, 
and,  occasionally,  chronic  interstitial  inflammation  were 
met  with.  Subsequently  Flexner  and  Pearce  showed 
that  the  introduction  of  artificial  gastric  juice  into  the 
duct  gave  rise  to  similar  changes,  but  that  injections  of 
sterile  blood,  while  they  occasioned  an  increase  of  fibrous 
tissue,  did  not  produce  acute  inflammatory  changes. 

Previous  to  these  experiments  by  Flexner  and  Pearce, 
acute  hsemorrhagic  pancreatitis  had  been  produced  in 
dogs,  by  Hlava,  from  injections  of  artificial  gastric  juice, 
and  he  suggested  that  the  cause  of  acute  pancreatitis  in 
man  lay  in  the  passage  of  hyperacid  gastric  juice  into  the 
pancreatic  duct  through  anti-peristaltic  action  in  the 
intestine.  There  is,  however,  no  evidence  which  would 
lend  support  to  such  a  view,  and  it  cannot  be  accepted 
as  a  likely  explanation. 

Hlava  and  Carnot,  as  well  as  Flexner,  have  induced 
acute  pancreatitis  by  injections  of  a  variety  of  bacteria, 
or,  in  some  instances,  of  their  toxines,  into  the  pancreatic 
duct,  and,  since  a  large  number  of  different  organisms  have 
been  isolated  from  the  pancreas  in  cases  of  acute  pancre- 
atitis, it  has  been  suggested  that  the  condition  is  depen- 
dent upon  bacterial  invasion  from  the  intestine.  It  is 
now  agreed  by  almost  all  writers  upon  the  subject  that 
the  bacteria  isolated  in  these  cases  have  no  etiological' 
connection  with  the  lesion  and  are  only  present  through 
secondary  invasion  of  the  injured  tissues. 

Hess  has  produced  necrosis,  with  hemorrhage  and  fat 
necrosis,  by  injections  of  olive  oil  into  the  pancreatic 
duct,  and  has  advanced  the  hypothesis  that  this  effect 


Pathology  143 

was  brought  about  by  the  products  into  which  the  oil 
was  split  by  the  steapsin  of  the  pancreatic  juice.  To 
verify  this  he  studied  the  effects  induced  by  injections  of 
fatty  acids,  soda-soap  solutions,  and  glycerine  into  the 
duct.  Oleic  acid,  and  4  per  cent,  soda-soap  solution, 
were  both  found  to  produce  the  same  result  as  the  oil, 
but  glycerine  failed  to  give  rise  to  any  acute  inflammatory 
changes.  In  consequence  of  the  results  obtained  in  these 
experiments  Hess  suggested  that  regurgitation  of  fatty 
substances  from  the  intestine,  favoured  by  widening  and 
injury  of  the  duodenal  orifice  of  the  common  duct  by  the 
passage  of  a  gall-stone,  was  a  possible  cause  of  human 
pancreatitis.  He  has  also  suggested  that  poisoning  with 
soap  might  be  the  cause  of  death  and  of  the  symptoms  of 
intoxication  that  precede  it,  for  Munk  and  Freidenthal 
have  shown  that  the  injection  of  o.i  gram  of  soap  per 
kilo  of  body-weight  into  the  vessels  of  an  animal  brings 
about  collapse  and  death. 

More  recently  Guleke  has  succeeded  in  producing  acute 
pancreatic  necrosis  in  20  out  of  27  dogs  by  ligaturing  the 
pancreatic  duct  close  to  the  duodenum,  and  injecting  5 
per  cent,  of  oil  on  the  pancreatic  side  of  the  ligature. 
In  the  majority  death  took  place  six  to  twenty  hours  after 
the  operation,  but  in  three,  where  extensive  necrosis  was 
present,  the  fatal  termination  was  delayed  three  to  six 
days.  In  seven  of  the  animals  no  effect  was  observed 
for  seven  to  ten  days.  They  then  had  loss  of  appetite, 
became  emaciated,  had  fatty  stools,  and  died  seventeen 
to  twenty-one  days  after  the  operation,  excepting  one 
strong  young  animal,  which  survived.  Post-mortem 
the  pancreas  was  found  to  present  characters  closely 
simulating  those  seen  in  man  in  chronic  pancreatitis. 

Guleke  has  also  induced  acute  necrosis,  terminating  in 
death  in  twenty  to  thirty  hours,  by  injecting  oil  into  the 
arteries  supplying  the  pancreas,  thus  producing  artificial 
infarcts. 


144       The  Pancreas:  Its  Surgery  and  Pathology 


The  association  of  diseases  of  the  pancreas  with  morbid 
conditions  of  the  biliary  passages  has  been  pointed  out  by  a 
number  of  observers,  and  since  in  most  individuals  the 
common  bile-duct  and  pancreatic  duct  unite  to  form  a 
common  channel  before  entering  the  duodenum,  and,  in 
many  persons  (62  per  cent.,  Helly),  the  common  duct  is 
embedded  in  the  tissue  of  the  pancreas  for  a  part  of  its 
course,  such  a  connection  is  probable  on  anatomical 
grounds.     The  possibility  that  a  gall-stone  lodging  in  the 

diverticulum  of  Vater  might 
produce  conditions  favour- 
able to  the  passage  of  mi- 
cro-organisms into  the  pan- 
creas was  suggested  by 
Lancereaux,  but  that  such 
an  event  might  also  bring 
about  the  penetration  of 
bile  into  the  pancreatic 
duct  was  first  clearly  dem- 
onstrated by  Opie. 

In  an  autopsy  on  a  case 

of  acute  pancreatitis  under 

Halstead's  care  Opie  found 

a  small  gall-stone  impacted 

the  duodenal   orifice   of 


Fig.  60. 


60    and 


■  Figs 
Diagram  to  show  how  a  small 
gall-stone  may  obstruct  the  pa- 
pilla, and,  if  the  ampulla  of  Vater 
be  very  large,  may  convert  the 
common  bile-duct  and  duct  of 
Wirsung  into  one  canal,  thus  pre- 
disposing to  acute  pancreatitis. 
Fig.  6 1 ,  Diagram  to  show  a  method 
of  termination  of  the  ducts  which 
will  not  predispose  to  pancreatitis 
(Opie). 


m 


the  ampulla  of  Vater, 
which,  while  too  large  to 
pass  into  the  duodenum,  was  yet  too  small  to  fill  the 
diverticulum  and  close  the  opening  of  the  pancreatic 
duct.  The  bile  and  pancreatic  ducts  were  thus  converted 
into  a  continuous  channel,  and  that  the  contents  of  the 
former  had  passed  into  the  duct  of  Wirsung  was  shown 
by  its  walls  being  deeply  stained  with  bile.  Investigat- 
ing the  literature  of  the  subject  Opie  collected  thirty- 
nine  cases  of  acute  pancreatitis  associated  with  gall-stones, 
situated  either  in  the  gall-bladder  or  in  the  bile-ducts. 


Pathology  145 

and  in  eight  of  these  he  found  that  there  was  a  calculus 
in  the  diverticulum  of  Vater.  It  appeared  possible, 
therefore,  that  the  entrance  of  bile  into  the  pancreatic 
duct  was  the  cause  of  the  pancreatitis  in  a  considerable 
proportion  of  cases.  In  attempting  to  verify  this  ex- 
perimentally, Opie  showed  that  the  injection  of  5  c.c. 
of  bile  into  the  pancreatic  duct  of  dogs  set  up  acute 
inflammatory  changes,  which  in  some  instances  were  fatal 
within  twenty-four  hours. 

While  claiming  that  bile  diverted  into  the  pancreatic 
duct  by  a  biHary  calculus  had  thus  been  shown,  both  clin- 
ically and  experimentally,  to  be  capable  of  producing  acute 
pancreatitis,  Opie  pointed  out  that  it  could  not  be  demon- 
strated that  all  cases  of  acute  pancreatitis  w^ere  dependent 
upon  this  cause.     Such  an  effect  can  take  place  only  when 
the  gall-stone  is  very  small,  and  the  anatomical  conditions 
of  the  duodenal  orifice  and  of  the  diverticulum  of  Vater  are 
favourable.     Measurement  of  the  diverticulum  of  Vater 
by  Opie  proved  that  in  about  30  per  cent,  of  cases  a  small 
calculus  could  probably  lodge  in  the  opening  of  the  diver- 
ticulum and  yet  only  partially  fill  the  cavity,  and,  as  in 
one  out  of  ten  individuals  the  bile-duct  joins  the  smaller 
pancreatic  duct,  while  the  larger  duct  of  Santorini  enters 
the  duodenum  at  the  site  of  the  lesser  papilla,  the  neces- 
sary anatomical  conditions  are  present  in  but  a  small 
proportion  of  cases,  and  the  rarity  of  acute  pancreatitis 
from  this  cause,  when  compared  with  the  relative  fre- 
quency of  cholelithiasis,  is  not  difficult  to  explain.     It 
has  been  shown  by  more  than  one  observer  that  the 
lower  end  of  the  biliary  passage  in  the  dog  is  normally 
the  habitat  of  pyogenic  bacteria,  and  it  has  been  suggested 
by  Trevor  that  the  experimental  injection  of  bile,  and 
other  substances,  into  the  pancreatic  duct  may  produce 
its  effect  by  lowering  the  resistance  of  the  walls  of  the 
duct,   thus   allowing  the   entrance   of  septic   organisms. 
Recent  experiments  by  Flexner,  however,  tend  to  prove 


146       The  Pancreas:  Its  Surgery  and  Pathology 


that  the  inflammatory  changes  are  directly  due  to  the 
action  of  the  bile  salts  upon  the  pancreatic  cells,  and  it  is 
probable  that  other  irritating  substances  may  act  in  a 
similar  manner. 

The  experimental  evidence  already  quoted  has  demon- 
strated that  the  injection  of  various  substances  into  the 
pancreatic  duct,  or  tissue  of  the  pancreas,  gives  rise  to 


Fig.  62. — Acute  haemorrhagic  necrosis  (above).  Zone  of  leucocytes  and 
red  cells,  acini,  swollen  and  cloudy  (below)  (Deaver  and  MuUer). 

acute  changes  which,  in  many  instances,  are  accompanied 
by  an  effusion  of  blood,  thus  giving  rise  to  what  is  clini- 
cally termed  " hcsmorrhagic  pancreatitis.''  In  some  in- 
stances, however,  where  the  animal  has  survived  for  a 
more  or  less  lengthy  period  we  have  seen  that  purulent 
changes,  or  necrosis  of  portions  of  the  gland  substance, 
have  been  found.     These  may  be  regarded  as  correspond- 


Pathology  147 

ing  to  suppurative  and  gangrenous  pancreatitis  respec- 
tively as  met  with  in  man.  It  would  therefore  appear 
that  hemorrhagic,  purulent,  and  gangrenous  pancreatitis, 
in  spite  of  the  differences  in  their  morbid  appearances,  are 
probably  but  phases  in  the  same  process,  and  that,  as 
Opie  has  remarked,  gangrenous  pancreatitis  is  but  a  late 
stage  of  the  hsemorrhagic  form. 

The  pancreas  in  hcemorrhagic  pancreatitis  is  enlarged ; 
its  interstitial  tissue,  as  well  as  the  tissues  in  its  neigh- 
bourhood, is  infiltrated  with  blood.  Microscopically 
the  parenchyma  is  necrotic  and  infiltrated  with  cellular 


Fig.  63. — Abscess  of  the  pancreas  (Roval  College  of  Surgeons  Museum 

2832).' 

and  fibrinous  exudates.  Numerous  foci  of  disseminated 
fat  necrosis  are  always  found  in  the  omentum  and  sub- 
peritoneal tissue. 

In  suppurative  pancreatitis  the  gland  contains  one  or 
more  abscess  cavities  of  varying  size.  It  may  be  enlarged, 
from  the  accompanying  inflammatory  changes,  and  the 
surrounding  tissue  may  be  indurated  and  adherent. 
The  history  of  suppurative  pancreatitis  is  always  much 
longer  than  that  of  the  hsemorrhagic  form,  as  the  results 
of  animal  experiments  would  suggest,  and  may  extend 
to  weeks  or  even  months. 

Gangrenous  pancreatitis  rarely  proves  fatal  until  some 


148       The  Pancreas:  Its  Surgery  and  Pathology 

little  time  after  the  first  onset  of  the  symptoms.  The 
organ  after  death  is  dry  and  dark,  or  even  black,  and  is 
enlarged  and  friable.  If  the  process  extends  to  the  sur- 
rounding tissues,  and  affects  the  lesser  peritoneal  sac, 
this  may  be  converted  into  an  abscess  cavity  containing 
pus  and  necrotic  material,  in  which  the  remains  of  the 
gangrenous  pancreatic  tissue  lie.  In  about  half  the 
recorded  cases  there  has  been  evidence  of  previous  hemor- 
rhage in  the  altered  gland,  which  points  to  its  frequently 
being  the  result  of  hasmorrhagic  pancreatitis  in  man, 
as  in  animals.  Disseminated  fat  necrosis  is  constantly 
found  in  gangrenous  pancreatitis,  but  is  uncommon  in  the 
suppurative  form. 

In  the  past  considerable  importance  has  been  attributed 
to  the  action  of  trypsin  in  the  production  of  necrosis  and 
other  pathological  conditions  in  the  pancreas,  but,  as 
the  pancreatic  secretion  is  now  known  to  have  but  slight 
proteolytic  powers  until  it  has  been  activated  by  the 
enterokinase  of  the  succus  entericus,  and  there  exist  in 
the  blood  anti-bodies  to  both  trypsin  and  enterokinase, 
this  explanation  cannot  now  be  considered  as  of  much 
weight.  Trypsin  poisoning,  however,  is  considered  by 
Guleke  to  be  the  true  cause  of  death  in  acute  necrosis  of  the 
pancreas.  He  found  that  if  the  pancreas  from  one  dog  is 
introduced  into  the  abdominal  cavity  of  another,  the 
same  clinical  symptoms  and  intra-abdominal  picture, 
excepting  for  the  local  condition  of  the  dog's  own  pan- 
creas, are  produced  as  are  seen  in  cases  of  acute  necrosis. 
He  also  found  that  constitutional  symptoms  resembling 
those  seen  in  acute  necrosis  were  induced  by  intravenous, 
intraperitoneal,  or  subcutaneous  injections  of  trypsin, 
but  that  if  the  animal  were  immunised  against  trypsin  by 
gradually  increasing  doses,  the  introduction  of  an  extir- 
pated pancreas  into  the  abdominal  cavity  was  not  so 
rapidly  fatal  as  in  unimmunised  animals. 

A  question  that  has  been  much  debated  is  the  rela- 


Pathology  149 

Hon  of  pancreatic  hcemorrhage  to  acute  pancreatitis.  Two 
possibilities  present  themselves:  (i)  that  the  haemorrhage 
is  a  consequence  of  the  inflammation;  (2)  that  the 
haemorrhage  is  the  primary  factor  and  the  inflammatory 
changes  secondary  phenomena.  Fitz,  Orth,  Birch-Hirsch- 
feld,  Zeigler,  Korte,  and  most  modern  writers  on  the 
subject  hold  that  the  inflammation  precedes  the  haemor- 
rhage, and  the  first  named  has  in  consequence  designated 
the  disease  "  hasmorrhagic  pancreatitis."  Dieckhoff,  Seitz, 
and  Hawkins  maintain,  on  the  other  hand,  that  the 
haemorrhage  precedes  the  inflammation,  which  is,  in  fact, 
caused  by  a  bacterial  infection  of  the  haemorrhagic  effu- 
sion. Seitz  considers  that  in  the  cases  recorded  by  Fitz 
and  others  as  examples  of  hccmorrhagic  pancreatitis, 
conclusive  evidence  in  proof  of  their  conclusions  was  not 
offered  in  a  single  instance,  and  he  further  contends  that 
if  the  haemorrhage  were  secondary  to  the  inflammatory 
changes  cases  would  from  time  to  time  occur  in  which 
there  was  a  rapidly  fatal  inflammation  without  haemor- 
rhage. Cayley  has  since  reported  a  case,  presenting 
symptoms  of  acute  pancreatitis,  which  was  fatal  on  the 
fourth  day,  and  on  post-mortem  examination  the  pan- 
creas was  said  to  show  evidence  of  acute  inflammatory 
changes.  There  was  neither  haemorrhage  nor  suppura- 
tion in  the  gland,  but  a  general  infiltration  with  blood- 
coloured  serum  in  and  around  it.  From  this  case  Cayley 
argues  that  hsemorrhage  is  not  an  essential  feature  of 
acute  pancreatitis.  A  similar  case  which  proved  fatal 
forty-eight  hours  after  the  first  onset  of  the  symptoms 
has  also  been  recorded  by  Kennan.  The  pancreas  in 
his  case  was  markedly  enlarged  from  inflammatory 
changes,  the  common  bile-duct  and  the  gall-bladder  con- 
tained numerous  gall-stones,  and  a  calculus  the  size  of  a 
pea  was  found  in  the  duodenum. 

A  study  of  the  reported  cases  of  "haemorrhagic  pan- 
creatitis," and  of  those  we  have  had  the  opportunity  of 


150       The  Pancreas:  Its  Surgery  and  Pathology 

ourselves  observing,  suggests  that  both  views  may  be 
correct  in  different  cases,  for  although  a  primary  pan- 
creatitis may  be  accompanied  by  haemorrhage,  this  origin 
is  not  the  only  one,  and  there  are  many  cases  in  which 
haemorrhage  precedes  and,  in  fact,  is  a  cause  of  inflam- 
mation. This  is  due,  first,  to  the  great  tendency  of  the 
gland  to  disruption,  because  of  its  soft  structure,  when 
haemorrhage  does  occur;  secondly,  to  the  communication 
of  the  gland  with  the  intestine,  which  renders  the  access 
of  putrefactive  organisms  likely;  thirdly,  to  the  great 
tendency  of  the  damaged  gland  and  effusion  to  decom- 
pose as  soon  as  organisms  gain  access  to  them.  This 
view  of  the  subject  has  at  least  the  merit  of  simplicity, 
and  br  ngs  "haemorrhagic"  pancreatitis  into  line  with 
other  well-known  inflammations. 

Suppurative  pancreatitis  and  abscess  of  the  pancreas 
are  sometimes  met  with  as  the  result  of  extension  from 
neighbouring  organs,  and  more  particularly  from  the 
stomach.  Dieckhoff  has  reported  a  case  of  secondary 
suppuration  associated  with  cancer  of  the  duodenum, 
and  Hale  White  speaks  of  an  instance  of  abscess  of  the 
head  of  the  gland  in  a  patient  who  died  of  a  malignant 
growth  of  the  sigmoid  flexure. 

Pycemic  abscesses  of  the  pancreas  are  rare,  but  have 
been  met  with  in  cases  of  pyaemia  and  puerperal  fever. 
Lancereaux  refers  to  a  case  of  abscess  of  the  pancreas 
due  to  the  pneumococcus. 

The]_injection  of  foreign  substances  into  the  parenchyma 
and  ducts  of  the  pancreas  in  some  instances,  instead  of 
giving  rise  to  the  acute  changes  already  described,  causes 
local  or  general  induration  of  the  gland,  accompanied  by 
an  overgrowth  of  the  interstitial  tissue.  Korte  found 
that  injections  of  oil  of  turpentine  caused  very  intense 
interstitial  changes,  and  Oser  showed  that  indurative 
pancreatitis  followed  the  injection  of  alcohol  and  zymine 
into   the   parenchyma.     Flexner   produced   sclerosis   by 


Pathology  151 

injecting  3  per  cent,  agar  into  the  pancreatic  ducts, 
and  in  seven  out  of  twenty-seven  dogs,  Guleke,  as  we 
have  seen,  induced  chronic  pancreatitis  by  injecting  oil 
into  the  ligatured  pancreatic  duct.  Two  animals  were 
also  injected  by  the  last-named  observer  with  blood  drawn 
from  the  femoral  vein ;  both  showed  signs  of  pancreatitis ; 
one  recovered,  but  the  other  died  of  chronic  pancreatitis 
in  three  weeks.  Korte  and  Senn  produced  indurative 
pancreatitis  by  injury  of  the  pancreas,  and  Sandmeyer 
has  found  that  sclerotic  changes  take  place  in  the  portions 
of  pancreatic  tissue  left  after  partial  extirpation.  Evi- 
dences of  chronic  inflammatory  changes  also  develop 
early,  according  to  Flexner,  around  acute  lesions  in  dogs. 
The  overgrowth  of  connective  tissue  caused  by  oil  of 
turpentine  is  said  by  Korte  to  be  increased  by  crushing, 
tearing,  or  cutting  the  gland. 

The  part  played  by  micro-organisms  in  the  production  of 
chronic  pancreatitis  has  been  investigated  by  Korte  and 
Carnot.  The  former  demonstrated  that  injections  of 
pure  cultures  of  bacillus  coli  caused  more  or  less  extensive 
interstitial  changes,  and  that  f cecal  matter  gave  rise  to 
similar  results,  Carnot,  by  an  ingenious  device,  produced 
sclerosis  of  the  pancreas  from  an  ascending  infection  from 
the  duodenum.  A  thread  was  fixed  in  the  pancreatic 
duct  and  carried  through  its  orifice  into  the  duodenum, 
where  it  was  allowed  to  hang  free,  and,  when  the  animal 
was  subsequently  killed,  the  walls  of  the  duct  were  found 
to  be  infiltrated  with  leucocytes  and  thickened,  while 
there  was  a  well-marked  overgrowth  of  the  interstitial 
tissue  in  the  gland  parenchyma. 

The  ascending  infection  from  the  duodenum  thus  dem- 
onstrated by  Carnot  as  a  possible  cause  of  chronic  pan- 
creatitis is  no  doubt  operative  in  man  under  certain 
circumstances,  since  a  history  of  dyspepsia  and  intestinal 
derangement,  with  or  without  vomiting,  is  not  uncommon 
in  this  disease.     The  changes  in  the  pancreatic  functions 


152       The  Pancreas:  Its  Surgery  and  Pathology 

thus  brought  about  are  probably  responsible  for  the 
continuance  of  many  cases  of  chronic  dyspepsia  in  which 
the  relation  is  not  usually  recognized,  for,  while  the  changes 
in  the  pancreas  may  be  initiated  by  pathological  condi- 
tions in  the  intestine,  the  diseased  pancreas,  not  being 
capable  of  properly  performing  its  functions,  will  accen- 
tuate and  prolong  any  digestive  disturbances  that  may 
be  present. 

The  entrance  of  micro-organisms  into  the  duct  of  Wir- 
sung  is  normally  prevented  by  the  flow  of  the  secretion 
and  the  valve-like  folds  in  the  walls  of  the  diverti- 
culum of  Vater,  but  the  duct  of  Santorini  is  not  thus 
protected,  for,  according  to  Desjardins,  the  secretion  may 
there  flow  indifferently  towards  the  intestine  or  from 
the  intestine  towards  the  gland.  Organisms  carried  in 
from  the  duodenum  by  a  reverse  current  will  be  conveyed 
through  the  substance  of  the  organ  to  the  point  where  the 
ducts  of  Santorini  and  Wirsung  are  connected,  and  there, 
meeting  with  the  direct  current  in  the  main  duct,  will  be 
carried  into  the  intestine  again.  These  circumstances 
would  naturally  favour  the  infection  of  the  gland,  and 
particularly  the  head,  when  from  any  cause  the  virulence 
of  the  intestinal  organisms  is  increased,  or  the  resistance 
of  the  pancreatic  tissue  is  lowered.  The  area  of  the  pan- 
creas enclosed  between  the  duodenum  to  the  right,  the 
duct  of  Santorini  above,  and  the  duct  of  Wirsung  below, 
has  been  termed  the  "  triangle  of  infection  of  the  pancreas, '  '■ 
and  represents  the  most  frequent  site  of  inflammatory 
changes  in  the  gland. 

Chronic  pancreatitis  is  produced  experimentally  with 
the  greatest  degree  of  certainty,  and  is  found  most  com- 
monly in  man,  as  a  consequence  of  obstruction  of  the 
ducts.  Pawlow  has  produced  interstitial  pancreatitis  in 
rabbits  by  ligature  of  the  pancreatic  duct;  Langendorff 
has  obtained  similar  results  in  pigeons ;  Schulze,  working 
with  guinea-pigs,  Ssobolew  with  rabbits,  dogs,  and  cats, 


Pathology 


153 


Opie  and  other  observers  with  cats  and  dogs,  have  also 
produced  an  overgrowth  of  connective  tissue  in  the  pan- 
creas by  a  similar  method.  The  pathogenesis  of  the  condi- 
tion is  not,  however,  quite  clear.  Carnot  has  suggested 
that  the  retained  secretion  has  a  toxic  effect  upon  the 
parenchyma  of  the  gland,  and,  since  the  obstruction  of 
the  flow  will  favour  the  entrance  of  micro-organisms  from 
the  duodenum,  chronic  inflammatory  changes  are  set  up 
which  result  in  disappearance  of  the  secreting  cells  and  an 
increase  of  the  inter- 
stitial connective  tis- 
sue. He  has  also  sug- 
gested that  the  re- 
flex nervous  stimuli 
which  were  believed 
to  give  rise  to  the 
pancreatic  secretion 
were  no  longer  able  to 
excite  normal  func- 
tional activity  when 
the  ducts  were  ob- 
structed, so  that  the 
cells  might  atrophy 
as  muscle  fibres  do 
after  section  of  their 
motor    nerve.       The 

discovery  of  secretin,  while  it  has  deprived  this  hypothe- 
sis of  the  basis  on  which  it  was  founded,  has  not  altogether 
disposed  of  it,  for  it  is  conceivable  that  the  constant 
stimulation  of  the  cells  by  secretin  may  eventually  give 
rise  to  atrophy  when  they  are  working  against  a  pressure 
that  they  cannot  overcome,  in  a  similar  manner  to  that 
in  which  the  kidney  undergoes  changes  in  obstruction  of 
the  ureter. 

Clinical  observation  has  shown  that,  although  chronic 
pancreatitis  may  arise  from  obstruction  of  the  duct  due 


Fig.  64. — Chronic  interstitial  pan- 
creatitis in  a  cat  following  ligation  of  the 
pancreatic  ducts  (Opie). 


154       The  Pancreas:  Its  Surgery  and  Pathology 


to  the  pressure  of  tumours,  stenosis  of  the  duodenal 
orifice  following  ulceration,  growth  in  the  duodenal  pap- 
illa or  ampulla  of  Vater,  and  the  presence  of  impacted 
pancreatic  calculi,  intestinal  worms,  or  portions  of  hy- 
datid membrane  in  the  duct,  it  is  most  commonly  asso- 
ciated with  cholelithiasis.  The  great  practical  importance 
of  the  association,  and  the  frequency  with  which  inflam- 
matory enlargement 
of  the  head  of  the 
gland  accompanies 
gall-stone  trouble, 
were  first  brought 
to  the  notice  of  the 
profession  in  a  lec- 
ture delivered  by 
one  of  us  at  the 
London  Polyclinic 
in  July,  1900,  and 
it  was  then  shown 
that  surgical  treat- 
ment is  capable  of 
affording  complete 
relief  in  nearly  all 
cases.  It  has  since 
been  pointed  out 
that  Riedel  had 
published,  in  1896, 
an  account  of  three 
cases  in  which  he  drew  attention  to  the  relation  of  chronic 
pancreatitis  to  cholelithiasis,  but  we  were  unacquainted 
with  his  work  at  the  time  this  lecture  was  given,  and  his 
observations  do  not  appear  to  have  attracted  notice  until 
after  that  date.  The  first  case  of  chronic  pancreatitis 
actually  operated  on  was  by  one  of  us  in  June,  1890,  the 
patient  being  alive  and  well  in  1905.  In  this  instance 
the   pancreas   was   enlarged   and   hard,    and   malignant 


Fig.  65. — Cancer  of  the  duodenal  pap- 
illa, with  dilatation  of  duct  of  Wirsung  and 
chronic  pancreatitis  (St.  George's  Hosp. 
Museum,  113  K). 


Pathology 


155 


disease  was,  at  the  time,  suspected,  but  her  ultimate  com- 
plete recovery  suggested  the  true  explanation.  In  April, 
1892,  however,  a  case  was  operated  on  in  which  the  con- 
dition was  proved  by  microscopical  examination,  and 
this,  which  was  investigated  a  year  before  Riedel's  first 
case,  in  1893,  is,  so  far  as  we  can  find,  the  earliest  instance 
where  chronic  pancreatitis  was  conclusively  demon- 
strated. A  large  number  of  cases  are  now  on  record  in 
which  various  surgeons 
have  observed  induration 
of  the  head  of  the  pan- 
"creas  associated  with  gall- 
stones. The  published 
cases  cannot,  however,  be 
taken  as  truly  represent- 
ing the  frequency  of  the 
condition,  for,  in  our  ex- 
perience, pancreatitis  is 
met  with  in  about  60  per 
cent,  of  cases  in  which 
gall-stones  are  found  in 
the  common  bile-duct  at 
operation. 

The  reason  for  the  asso- 
ciation of  the  two  condi- 
tions is  not  difficult  to 
understand,      when      the 

anatomy  of  the  parts  is  considered.  Under  ordinary  cir- 
cumstances, when  a  gall-stone  passes  along  the  common 
bile-duct  and  reaches  the  ampulla  of  Vater  it  will  not 
only  occlude  the  bile-passage,  but  also  the  chief  excretory 
duct  of  the  pancreas,  the  secretion  of  which  will  be  re- 
tained. An  infection  of  the  retained  secretion,  of  tjie 
walls  of  the  ducts,  and  of  the  parenchyma  of  the  gland, 
is  then  likely  to  occur,  and  this  will  continue  so  long  as 
the  obstruction  persists. 


Fig.  66. — Gall-stone  in  the  com- 
mon bile-duct  surrounded  by  the 
head  of  the  pancreas  (St.  Thomas' 
Hospital  Museum,  1380). 


156       The  Pancreas:  Its  Surgery  and  Pathology 

How  far  the  pancreatic  lesion  in  these  cases  is  to  be 
attributed  to  the  irritating  action  of  the  retained  secre- 
tion, and  how  far  to  the  associated  bacterial  infection, 
it  is  difficult  to  say;  but  it  is  probable  that,  while  the 
former  damages  the  tissues  of  the  gland  and  renders 
them  susceptible  to  infection,  the  process  is  chiefly  due 
to  the  action  of  micro-organisms.  Even  when  the  block- 
ing of  the  ducts  is  complete  and- no  direct  communication 
between  the  micro-organisms  in  the  duodenum  and  the 
stagnant  secretion  is  possible,  the  inflamed  walls  of  the 
duct  present  a  ready  path  by  which  infection  may  travel 
from  the  intestine,  and  that  this  does  occur  in  the  bile 
passage  has  been  proved  by  aseptic  ligature  of  the  com- 
mon duct.  Absolutely  complete  blocking  of  the  duct  is, 
however,  very  uncommon,  except  in  cancer  of  the  head 
of  the  pancreas,  for,  as  we  shall  show  later,  bile-pigment 
can  be  found  chemically  in  the  fasces  in  nearly  all  cases, 
even  when  the  stools  appear  free  from  colour  to  the  eye. 

Another  route  by  which  infection  may  reach  the  duct 
of  Wirsung  and  biliary  passages  has  been  suggested  by 
Desjardins.  We  have  already  pointed  out  how,  in  his 
opinion,  organisms  normally  find  their  way  from  the 
duodenum  along  the  duct  of  Santorini  into  the  main  pan- 
creatic duct,  and  thence  into  the  ampulla  of  Vater  and 
back  to  the  duodenum  again,  and  it  is  by  this  route,  he 
believes,  that  infection  of  the  biliary  passages  and  pan- 
creas takes  place  when  there  is  obstruction  from  gall- 
stones. The  first  effect  produced  by  the  lodging  of  a 
biliary  calculus  in  the  ampulla  of  Vater,  or  lower  part  of 
the  common  bile-duct,  will  be  that  the  septic  organisms, 
arriving  by  way  of  the  duct  of  Santorini  and  thence  passing 
into  the  duct  of  Wirsung,  will  be  unable  to  travel  into  the 
duodenum,  and,  being  arrested  in  the  biliary  passages  and 
pancreatic  ducts,  will  there  set  up  inflammatory  changes. 
As  the  pancreatic  ducts  are,  however,  more  or  less  immune, 
from  the  constant  presence  in  them  of  intestinal  organisms, 


Pathology  157 

the  chnical  symptoms  will,  in  the  first  place,  be  referred 
to  the  bile-passages,  the  pancreatic  ducts  and  the  head  of 
the  pancreas  not  being  markedly  affected  by  the  process 
until  they  are  attacked  by  bacteria  whose  virulence  has 
been  increased  by  growing  in  the  morbid  secretion  and 
diseased  tissues  of  the  bile-ducts.  Inoculation  and  re- 
inoculation  from  the  pancreas  to  the  biliary  passages, 
and  back  from  the  bile-ducts  to  the  pancreas,  will  then 
occur,  so  that  the  pancreatic  lesion  will  continually  pro- 
gress so  long  as  the  obstruction  is  unrelieved.  This 
hypothesis  has  been  accepted  by  Quenu  and  Duval. 
While  not  denying  that  it  is  in  some  instances  possible, 
we  would  point  out  that,  according  to  the  observations 
of  Opie  upon  the  ducts,  it  is  unlikely  that  infection  of  the 
retained  secretions  and  walls  of  the  ducts  can  take  place 
in  the  manner  suggested  in  at  least  31  per  cent,  of  cases, 
for  Opie  found  that  in  21  per  cent,  of  the  bodies  he  exam- 
ined the  duct  of  Santorini  was  impervious,  and  in  10  per 
cent.,  where  a  through  channel  existed,  the  duct  of  Wir- 
sxing  did  not  anastomose  with  the  duct  of  Santorini. 

In  a  valuable  paper  on  "The  Constituent  of  Bile  Caus- 
ing Pancreatitis"  Flexner  has  given  an  account  of  a  num- 
ber of  experiments  which  throw  considerable  light  upon 
the  relation  of  cholelithiasis  to  both  chronic  and  acute 
pancreatitis.  He  found  that  solutions  of  purified  bile 
salts  when  injected  into  the  pancreatic  duct  of  animals 
gave  rise  to  acute  fatal  haemorrhagic  and  gangrenous 
inflammation  of  the  gland,  with  fat  necrosis,  but  that  the 
mucigenous  residue  from  dog-bile,  precipitated  out  by 
alcohol,  when  similarly  injected  produced  no  lesion  in 
seventeen  days,  except  that  there  was  slight  sclerosis, 
probably  from  ligature  of  the  duct.  It  was  therefore 
evident  that  the  effect  of  the  injection  of  bile  was  due  to 
the  bile  salts.  On  mixing  the  bile  salts  with  the  mucige- 
nous residue,  the  lesion  produced  by  injection  was  found 
to  be  of  a  less  acute  and  destructive  character  than  that 


158       The  Pancreas:  Its  Surgery  and  Pathology 

following  the  injection  of  bile  salts  alone.  A  similar 
result  was  obtained  when  agar  and  gelatine  were  substi- 
tuted for  the  mucoid  material.  The  action  of  the  bile 
salts  appeared  therefore  to  be  restrained  by  mixing  it 
with  colloid  substances.  Experiments  with  gelatine  and 
bile  salts  showed  that  if  the  colloid  was  readily  attacked 
by  the  pancreatic  juice,  so  that  the  salts  were  brought 
rapidly  into  contact  with  the  gland  tissue,  a  moderately 
severe  lesion  resulted;  whereas,  with  a  substance  such  as 
agar,  which  is  little,  if  at  all,  altered  by  the  pancreatic 
secretion,  the  effect  of  the  bile  salts  was  exerted  so  slowly 
that  all  gross  injury  of  the  pancreatic  substance  was 
avoided.  Increasing  the  colloid  strength  of  bile,  or  of 
solutions  of  bile  salts,  by  the  addition  of  mucin,  nucleo- 
proteid,  or  even  by  diluting  with  normal  saline,  was  found 
to  modify  the  intensity  of  the  lesion  in  a  similar  way  to 
gelatine  and  agar,  so  that  the  pancreas  might  altogether 
escape  injury  from  a  quantity  of  bile  salt  which  would 
otherwise  have  caused  a  severe  and  rapidly  fatal  condi- 
tion. 

Flexner  concludes  from  these  experiments  that  when 
the  composition  of  the  bile  is  modified  by  a  diminution 
of  its  salts  or  an  increase  of  colloid  material,  its  pas- 
sage into  the  pancreatic  duct  is  likely  to  set  up  chronic 
pancreatitis,  but  when  fresh  unaltered  bile  gains  entry 
into  the  duct  of  Wirsung,  it  sets  up  acute  changes.  He 
points  out  that  in  obstruction  of  the  biliary  passages  there 
is  a  loss  of  diffusible  salts  and  an  increase  of  colloid  mate- 
rial, and,  further,  that  inflammation  of  the  passages 
causes  an  accumulation  of  albuminous  products,  so  that 
by  both  means  the  composition  of  the  bile  is  altered  in  a 
direction  which,  according  to  his  experiments,  would 
tend  to  favour  the  production  of  chronic  changes  rather 
than  acute  and  fulminating  lesions  of  the  gland.  As  we 
have  already  said,  it  is  difficult  to  know  how  far  chronic 
changes   in  the   pancreas   in  common  duct   obstruction 


Pathology  1 59 

are  due  to  micro-organisms  and  how  far  to  mechanical 
and  purely  chemical  causes,  but  it  is  clear  from  Flexner's 
experiments  that  the  influence  of  the  bile  must  be  taken 
into  account.  Chronic  pancreatitis  is  often  associated 
with  very  small  stones,  so  that  it  is  possible  that  bile 
which  has  been  modified  by  inflammatory  changes  may 
have  been  diverted  into  the  pancreatic  duct  and  set  up 
chronic  inflammation  in  the  way  Flexner  suggests.  Even 
with  large  calculi  the  obstruction  is  rarely  so  complete 
that  bile  cannot  find  its  way  into  the  intestine,  and  possi- 
bly also  into  the  duct  of  Wirsung,  and  there,  by  its  toxic 
action,  it  may  predispose  the  tissues  to  the  action  of 
bacteria.  When  the  pancreatic  duct  is  occluded,  secre- 
tion ceases  at  a  pressure  of  only  a  few  centimetres  of  water, 
owing  probably  to  the  ease  with  which  any  fluid  formed 
by  the  gland  cells  escapes  through  the  alveoli  into  the 
surrounding  lymph  spaces,  so  that  it  is  not  necessary  to 
suppose  that  any  great  amount  of  force  is  required  to 
carry  bile  or  other  fluids  into  the  ducts,  and  thence  into 
the  interstices  of  the  parenchyma.  The  diffusion  which 
naturally  occurs  in  a  stagnant  fluid  has  also  to  be  consid- 
ered in  this  connection.  That  the  entry  of  bile  is  not  the 
only  cause  of  the  interstitial  changes  that  are  commonly 
found  in  obstruction  of  the  ducts  is  shown,  however,  by 
the  effects  of  ligature,  or  of  introducing  such  substances 
as  agar  or  turpentine,  and  some  part  of  the  process  must 
no  doubt  be  attributed  to  the  altered  pancreatic  secretion 
itself. 

Morbid  influences  may  not  only  reach  the  pancreas  by 
way  of  the  ducts,  but  also  through  the  blood-vessels  and 
lymph  stream.  Pancreatitis  in  general  infectious  dis- 
eases is  not  common,  and  we  have  already  referred  to  the 
comparative  rarity  of  abscess  of  the  pancreas  in  general 
pyaemia.  The  pancreatitis  which  is  occasionally  met 
with  as  a  sequel  of  typhoid  fever  is  possibly  due  to  a 
specific  infection  travelling  up  the  ducts,  but  it  is  not 


i6o       The  Pancreas:  Its  Surgery  and  Pathology 

unHkely  that  it  may  arise  from  the  infection  of  the  blood 
which  is  now  known  to  be  always  present  in  that  disease. 
In  Moynihan's  case,  which  was  operated  on  a  year  and 
a  half  after  the  attack  of  fever,  typhoid  bacilli  were  iso- 
lated from  the  bile,  and  the  patient's  blood  gave  the 
Gniber-Widal  reaction  for  typhoid  fever.  Three  weeks 
later  typhoid  bacilli  were  still  present  in  the  bile,  but  at 
the  end  of  five  weeks  it  was  sterile.  This  observation, 
while  it  suggests  that  the  source  of  the  pancreatic  condi- 
tion lay  in  the  infected  state  of  the  bile,  due  to  the  passage 
of  typhoid  bacilli  up  the  bile-ducts  from  the  intestine, 
cannot  be  accepted  as  conclusively  settling  the  point, 
for  it  is  well  known  that  the  urine  may  contain  typhoid 
organisms  months,  and  even  years,  after  recovery  from, 
an  attack,  although  in  this  instance  the  infection  undoubt- 
edly reaches  the  kidneys,  and  through  them  the  urine, 
by  way  of  the  blood. 

Influenza  and  other  zymotic  diseases  are  also  occas- 
ionally followed  by  chronic  inflammation  of  the  pancreas. 
In  these  the  infection  is  probably  carried  by  the  blood, 
although  in  the  gastro-intestinal  form  of  influenza  direct 
infection  of  the  pancreas  through  its  ducts  may  take  place. 

An  attack  of  mumps  is  in  some  instances  complicated 
by  pancreatitis,  and  although  the  unknown  causal  agent 
is  probably  carried  from  one  to  the  other  by  the  blood- 
stream, the  connection  is  as  obscure  as  that  which  exists 
between  parotitis  and  orchitis. 

The  influence  of  alcohol  in  the  production  of  cirrhosis 
of  the  liver  is  still  a  debatable  point,  and  similarly  its 
relation  to  chronic  pancreatitis  has  not  been  settled.  In 
some  cases  a  history  of  alcoholism  can  be  obtained,  but 
this  is  not  common.  It  is  probable  that  alcohol  is  not 
itself  a  direct  determining  cause,  but  that,  indirectly,  by 
the  influence  it  exerts  upon  the  circulation,  and  by  a 
production  of  a  catarrh  of  the  duodenum,  it  may  give 
rise  to  pancreatitis. 


Pathology 


i6i 


The  chronic  infections,  syphilis  and  tubercle,  affect  the 
pancreas  through  its  blood  and  lymph  supply.  Both 
give  rise  to  changes  in  the  interstitial  tissue.  The  syphi- 
litic lesions  may  be  divided  into  those  met  with  in  con- 
genital syphilis,  and  those  occurring  in  the  acquired 
infection. 

Attention  was  first  drawn  to  the  frequency  with  which 
the  pancreas  is  affected  in  congenital  syphihs  by  Birch- 
Hirschfeld  in  1875,  and,  although  the  investigations  of 
Schlesinger,  and 

later    observa-  .  .r/-r''^'^'3«^'^'-  -v., 

tions  by  Birch- 

Hirschfeld   him-  ;•  .    "        ..   s 

self ,  have  shown  '•.       .,,.*■,;•;-■.;.' 

that  it  is  not  so 
common  as  he 
had  at  first  sup- 
posed, it  is  by 
no  means  un- 
common, and 
would  appear  to 
be  present  in 
about  22  or  23 
per  cent,  of  all 
cases  of  syphilis 
in  new-born  in- 
fants. The  con- 
dition, like  many 
other  syphilitic  lesions,  is  due  to  an  overgrowth  of  the 
interstitial  tissue,  which,  according  to  Schlesinger,  orig- 
inates about  the  blood-vessels.  The  inflammatory  new- 
growth  affects  both  the  interlobular  and  interacinar 
tissue,  and  occasionally  spreads  between  the  acinar  cells, 
which  atrophy  and  disappear  without  presenting  any  evi- 
dences of  degeneration.  In  the  two  cases  of  congenital 
syphilitic    pancreatitis    examined    by    Opie,    numerous 


Fig.  67. — Congenital  syphilitic  pancreatitis, 
with  almost  complete  destruction  of  the 
secreting  acini  and  persistence  of  the  islands 
of  Langerhans  (X  50)  (RoUeston's  case). 


1 62       The  Pancreas:  Its  Surgery  and  Pathology 

islands  of  Langerhans  were  present  in  the  thickened 
stroma,  and  some  were  found  to  be  in  connection  with 
the  secreting  structure  of  the  gland,  although  the  lumen 
of  the  duct  could  be  traced  no  further  than  the  periphery 
of  the  island.  Schlesinger  has  also  pointed  out  that  the 
islands  of  Langerhans  are  neither  invaded  by  the  new- 
growth  of  interstitial  tissue  nor  implicated  in  the  atrophy 
which  affects  the  cells  of  the  acini. 

Opie  mentions  that  the  parenchyma  in  his  cases  pre- 
sented the  appearance  observed  about  the  fifth  month 
of  development,  save  that  the  islands  of  Langerhans  were 
more  marked  features  in  the  syphilitic  glands.  An 
explanation  of  the  similarity  between  the  undeveloped 
and  syphilitic  organ  is  afforded  by  supposing  that  the 
development  of  the  individual  cell  is  not  retarded,  and 
that  the  changes  in  the  parenchyma  result,  not  so  much 
from  its  destruction,  as  from  interference  with  its  growth. 
The  islands  of  Langerhans  being  the  result  of  an  early 
cell-differentiation,  and  lying  more  or  less  in  the  centre 
of  the  masses  of  secreting  cells,  where  they  are  protected 
from  the  early  results  of  the  overgrowth  of  connective 
tissue,  develop  and  remain  unaffected  by  the  interstitial 
changes  until  a  late  stage  of  the  disease.  Birch-Hirsch- 
feld  believed  that  congenital  syphilitic  pancreatitis 
affected  the  organ  during  the  last  months  of  foetal  life, 
but  Schlesinger  concludes  from  a  study  of  his  own  cases, 
and  those  of  Mraczek  and  Miiller,  that  it  may  be  affected 
as  early  or  as  late  as  other  organs. 

Syphilitic  lesions  in  acquired  syphilis  are  much  rarer 
than  in  the  congenital  form  of  the  disease,  although 
Hansemann,  Kasahara,  and  other  writers  have  contended 
that  it  is  the  most  common  cause  of  chronic  pancreatitis. 
A  few  cases  of  indurative  pancreatitis,  due  to  acquired 
syphilis,  have  been  recorded,  but  the  condition  most 
frequently  met  with  is  the  penetration  of  the  parenchyma 
by   irregular   bands    of   scar-like   tissue   and   gummata. 


Pathology 


163 


Occasionally,  as  in  the  case  reported  by  Drozda,  the 
pancreas  may  be  converted  into  a  mass  of  indurated 
tissue  in  which  only  remains  of  the  gland  substance  can 
be  found.  Betham  Robinson  has  reported  a  case  of 
obstructive  jaundice  due  to  gummatous  infiltration  of 
the  head  of  the  pancreas,  in  which  cholecystcolostomy 
was  successfully  performed.  In  a  few  cases  of  congenital 
syphilis  minute  and  rarely  large  gum- 
mata  have  been  noticed. 

Tuberculosis  of  the  pancreas  arises 
practically  always  in  connection  with 
tuberculosis  in  other  organs,  the 
blood-vessels  furnishing  the  channel 
by  which  the  bacilli  are  distributed 
to  the  gland  in  the  majority  of  in- 
stances. Primary  tuberculosis  of  the 
pancreas  was  probably  present  in  a 
case  of  Senn's  described  by  Mayo, 
but  it  is  the  only  one  of  which  we 
can  find  any  record.  Multiple  small 
tuberculous  deposits  may  be  found 
irregularly  scattered  through  the  sub- 
stance of  the  gland,  or  single  large 
masses,  which  may  caseate  and  form 
cavities  that  open  into  adjacent  or- 
gans, such  as  the  stomach,  may  be 
met  with.  It  is  probable  that  the 
single  masses  originate  from  the 
lymph  glands  buried  in  the  substance 
of  the  organ,  for  such  a  mass  was 
successfully  removed  by  operation  from  the  head  of  the 
pancreas  by  Sendler,  and  on  microscopical  examination 
was  found  to  be  a  tuberculous  lymph  gland. 

According  to  Carnot,  diffuse  interstitial  pancreatitis 
is  more  commonly  associated  with  tuberculosis  of  other 
organs  than  is  the  specific  lesion  itself.     Cases  of  this 


Fig.  68.— Tuber- 
culosis of  the  pan- 
creas following  tu- 
berculous meningitis, 
showing  deposits  of 
tubercle  and  a  small 
abscess  cavity  (St. 
Bartholomew's  Hosp. 
Museum,  2272  A). 


1 64       The  Pancreas:  Its  Surgery  and  Pathology 

description  have  been  reported  by  Carnot,  Ancelet, 
Vulpian,  Arnozan,  Morache,  and  Opie.  There  is  usually 
a  moderate  degree  of  chronic  inflammation,  causing  an 
increase  of  the  connective  tissue  normally  present  around 
vessels  and  ducts  and  between  the  lobules.  By  injecting 
considerable  quantities  of  a  suspension  of  tubercle  bacilli 
into  the  ducts  and  parenchyma  of  the  pancreas  in  dogs 
Carnot  was  able  to  produce  caseous  abscesses  and  inflam- 
matory changes,  but  the  lesions  showed  none  of  the 
specific  characters  of  tuberculosis,  and  tubercle  bacilli 
were  not  found  in  the  tissues.  Inferring  from  these 
results  that  the  changes  noticed  might  be  due  to  the  action 
of  the  toxines  contained  in  the  organism,  he  injected 
tuberculin,  prepared  from  dead  bacilli,  into  the  paren- 
chyma of  the  gland,  and  obtained  in  one  instance  loca- 
lised sclerosis.  That  chronic  pancreatitis  may  be  caused 
by  chemical  products  elaborated  in  a  tuberculous  lesion 
is  also  suggested  by  cases  described  by  Carnot  and  Arno- 
zan. In  the  former  the  splenic  extremity  of  the  gland, 
in  contact  with  a  tuberculous  kidney,  was  alone  afi'ected, 
and  in  the  latter  chronic  pancreatitis  accompanied  tuber- 
culous peritonitis. 

Alterations  in  the  blood  supply  of  the  pancreas  are  another 
cause  of  chronic  interstitial  changes.  General  arterial 
sclerosis  and  endarteritis,  although  more  commonly 
associated  with  atrophy  and  fatty  degeneration,  some- 
times give  rise  to  chronic  interstitial  pancreatitis.  It  is 
possible  that  the  moderate  increase  of  fibrous  tissue  found 
microscopically  in  a  certain  number  of  patients  over 
forty  years  of  age  (lo  per  cent,  of  Bosanquet's  cases)  may 
be  due  to  this  cause.  Fleiner  suggests  that  the  condition 
is  similar  to  that  met  with  in  contracted  kidney,  and  in 
the  liver,  brain,  and  heart,  as  a  result  of  endarteritis 
obliterans.  Both  he  and  Hoppe-Seyler  think  that  the 
arterial  disease  causes  nutritive  changes  in  the  paren- 
chyma,  which   degenerates   and  is  replaced  by  fibrous 


Pathology  i6 


D 


tissue.  An  increase  of  the  connective  tissue  of  the  gland, 
especially  that  connected  with  the  veins  and  lymphatic 
vessels,  has  been  described  by  Lepine,  Abia,  Lemoine, 
and  Lannois.  In  these  cases  the  lobules  were  separated 
by  strong  trabeculse  of  connective  tissue  which  penetrated 
between  the  individual  cells.  In  spite  of  the  marked 
microscopical  changes  found,  it  is  noteworthy  that  no 
abnormality  of  the  pancreas  was  seen  on  naked-eye 
examination.  Long-standing  difficulty  of  venous  flow, 
due  to  chronic  disease  of  the  heart,  liver,  lungs,  etc.,  may 
cause  induration  and  fibrosis  of  the  pancreas,  as  of  other 
organs.  Thrombosis,  or  blocking  of  the  portal  vein  by 
growth,  has  also  been  met  with  as  a  cause  of  chronic 
changes  in  the  pancreas.  Basing  his  conclusion  on  the 
post-mortem  records  of  Guy's  Hospital,  Hale  White  is  of 
opinion  that  disturbances  of  circulation  are  much  com- 
moner than  other  causes  of  cirrhosis,  congestion,  or 
hardening  of  the  pancreas.  Opie,  however,  comes  to  the 
conclusion  that  chronic  passive  congestion  is  an  unimpor- 
tant factor  in  the  production  of  chronic  pancreatitis,  and 
in  our  experience  circulatory  disturbances  are  uncommon 
clinical  causes  of  pancreatic  troubles. 

Nearly  all  modern  observers  are  agreed  that  the  pan- 
creas is  frequently  affected  by  an  overgrowth  of  connective 
tissue  in  cirrhosis  of  the  liver.  In  cases  associated  with 
portal  cirrhosis  the  size  of  the  pancreas  varies.  It  is 
generally  enlarged  as  a  whole,  but  should  atrophy  recog- 
nisable by  the  naked  eye  be  present,  the  body  and  tail 
of  the  gland  are  the  parts  chiefly  affected.  Klippel  and 
Lefas  found  that  the  size  and  consistency  of  the  pancreas 
are  not  related  in  any  way  to  the  condition  present  in 
the  liver.  As  a  rule,  the  liver  is  more  seriously  affected, 
but  in  some  cases  the  disease  of  the  pancreas  is  in 
a  more  advanced  stage.  In  every  case,  however,  the 
fibrous  tissue  in  the  pancreas  was  fully  formed  and  poor 
in  nuclei,  even  when  the  newly  formed  fibrous  tissue  in 


1 66       The  Pancreas:  Its  Surgery  and  Pathology 

the  liver  was  of  a  semi-adult  type.  They  therefore  con- 
clude that  cirrhosis  of  the  liver  and  pancreas  are  due  to 
the  same  etiological  factors,  but  that  the  pancreatic 
condition  is  independent  of,  and  not  secondary  to,  the 
lesion  in  the  liver.  The  increase  of  fibrous  tissue  in.  the 
pancreas  is  perilobular,  intralobular,  or  partly  periaci- 
nous,  but  is  usually  chiefly  intralobular.  There  is  occa- 
sionally interlobular  oedema,  and  scattered  areas  of  small- 
celled  infiltration  are  met  with.  The  gland  cells  show 
fatty  and  pigmentary  changes,  but  the  islands  of  Langer- 
hans  are  unaffected. 

Although  the  pancreas  in  biliary  cirrhosis  is  not  gener- 
ally increased  in  size  or  weight,  it  is  often  indurated,  and 
may  be  united  to  neighbouring  organs  by  adhesions.  The 
fibrosis  is  of  an  embryonic  type,  and  appears  to  spread 
from  the  ducts.  The  acinar  cells  show  signs  of  fatty 
degeneration,  and  there  is  some  proliferation  of  the  cells 
lining  the  ducts.  Exceptionally  there  may  be  enlarge- 
ment of  the  pancreas  with  hypertrophic  cirrhosis  of  the 
liver,  when  there  is  also  extreme  enlargement  of  the 
spleen. 

Chronic  interstitial  pancreatitis  is  met  with  in  kcEmo- 
chromatosis.  In  this  condition  the  pancreas  is  enlarged, 
firm,  and  pigmented,  there  is  generally  hypertrophic 
cirrhosis  of  the  liver,  and,  in  the  majority  of  cases,  bronz- 
ing of  the  skin  also  occurs.  The  islands  of  Langerhans 
are  gradually  altered  or  destroyed,  and  diabetes  {diabetes 
bronze)  usually  supervenes  in  the  later  stages.  The  etio- 
logical factors  of  this  disease  are  not  known,  but  it  is  evi- 
dent that  they  simultaneously  produce  change  in  the  liver 
and  pancreas. 

Occasionally  chronic  inflammation  of  the  pancreas 
may  be  due  to  the  extension  of  inflammatory  processes 
from  neighbouring  organs.  The  most  common  origin  is 
from  a  gastric  ulcer  adherent  to  the  head  of  the  gland. 
Ulcers  of  the  duodenum,  and  ulcerating  malignant  growths 


Pathology  167 

of  the  pylorus,  have  also  been  responsible  for  the  condi- 
tion in  our  experience.  Cases  in  which  secondary  inflam- 
mation has  been  caused  by  ulcerating  growths  in  other 
organs,  by  pre- vertebral  inflammatory  processes,  and  by 
aneurysm  of  the  aorta  or  coeliac  artery,  have  been  re- 
corded. 

From  what  has  been  already  said  on  the  microscopical 
appearances  seen  in  chronic  pancreatitis  arising  from 
various  causes,  it  will  have  been  gathered  that  the  histo- 
logical changes  are  not  always  of  the  same  type.  A 
classification  of  the  various  forms  based  upon  etiological 
data  is,  in  the  present  imperfect  state  of  our  knowledge, 
unsatisfactory,  and  similarly  attempts  to  refer  the  origin 
of  the  fibrous  overgrow^th  to  the  ducts,  blood-vessels, 
and  lymph  channels  are  so  speculative  as  to  be  unreliable 
in  practice.  The  best  working  classification  is  that  first 
clearly  outlined  by  Opie.  This  observer  distinguishes 
two  main  types  of  chronic  interstitial  inflammation,  which 
can  be  distinguished  microscopically,  and  present  more  or 
less  different  characters  to  the  naked  eye.  In  the  first, 
or  ''interlobular''  type,  the  increase  of  connective  tissue, 
although  never  accurately  confined  to  one  locality,  is 
most  conspicuous  between  the  lobules,  and  affects  little, 
if  at  all,  the  intralobular  and  interacinous  trabeculae. 
The  normally  obscure  lobulation  of  the  gland  becomes 
more  conspicuous,  and  wide  bands  of  sclerotic  tissue 
separate  groups  of  lobtdes.  The  progress  of  the  lesion 
is  apparently  inward  from  the  periphery  of  the  lobules, 
which  are  invaded  to  a  greater  or  less  degree  by  the 
newly  formed  fibrous  tissue.  Often  entire  lobules  are 
seen  in  the  process  of  disintegration  and  replacement. 
The  islands  of  Langerhans  are  not  affected  until  a  late 
stage  of  the  disease  and  diabetes  does  not  occur,  except 
when  the  fibrosis  is  very  advanced.  Macroscopically  the 
gland  is  ha.rd  and  dense,  and  has  a  nodular  or  granular 
surface  when  the  lesion  is  well  marked.     On  section  the 


Fig.  69. — Microphotographs  of  the  pancreas  in  six  cases  of  chronic 
pancreatitis  under  our  care,  showing  the  stages  of  the  process:  (a)  Ca- 
tarrhal pancreatitis;  (6)  shght  interlobular  pancreatitis;  (c)  more  ad- 
vanced interlobular  fibrosis ;  (d)  advanced  interlobular  pancreatitis ;  (e) 
very  advanced  fibrosis;  (/)  cirrhosis  of  the  pancreas  from  a  case  of 
diabetes  (X  ca  42). 

168 


Pathology 


169 


loose  areolar  tissue,  normally  present  between  the  secon- 
dary and  tertiary  lobules,  is  found  to  have  been  replaced 
by  sclerotic  bands,  so  that  the  cut  surface  has  a  compact 
and  homogeneous  appearance. 

In  the  second,  or  "  inter  acinar''  type,  the  new-formation 
of  fibrous  tissue  takes  place  j)rimarily  within  the  lobules, 
is  of  a  diffuse  character,  and  forms  an  irregular  network 
of  fibrous  strands  of  varying  thickness  which  encloses 
the  gland  acini  in  its  meshes.  The  interlobular  tissue 
may  be  only  slightly 
altered.  The  islands 
of  Langerhans  are 
early  affected,  and 
diabetes  is  a  com- 
mon accompani- 
ment  of  the  condi- 
tion. The  organ  is 
usually  smooth  on 
the  surface,  and  in 
section  is  found  to 
be  tough  rather 
than  hard.  Well- 
marked  microscop- 
ical changes  may  be 
present,  in  either 
form,  however, 
without  there  being  any  noticeable  macroscopical  lesion. 

Calculi. — An  extreme  degree  of  sclerosis  is  often  found 
to  be  associated  with  the  presence  of  pancreatic  calculi  in 
the  ducts,  and  it  is  usually  assumed  that  the  pancreatitis 
is  a  result  of  the  blocking  and  irritation  of  the  ducts  by 
the  calculi.  Although  this  is  no  doubt  true  to  a  certain  ex- 
tent, and  the  very  marked  fibrosis  found  post-mortem  in 
such  cases  is  largely  due  to  the  presence  of  the  calculi,  it  is 
probable  that  the  concretions  themselves  arise  as  a  conse- 
quence of  morbid  changes  in  the  pancreatic  secretion  con- 


Fig.  70.— Interstitial  pancreatitis  in 
the  neighbourhood  of  an  adherent  gastric 
ulcer  (X  40). 


lyo       The  Pancreas:  Its  Surgery  and  Pathology 

nected  with  inflammatory  changes  in  the  glands  and  ducts. 
By  ligaturing  the  duct  of  Wirsung,  Pende  was  able  to  in- 
duce the  formation  of  pancreatic  calculi  in  a  considerable 
proportion  of  the  rabbits  on  which  he  operated.  The 
concretions  were  small,  and  none  were  discovered  until  a 
minimum  interval  of  twenty-eight  days  had  elapsed. 
They  consisted  of  a  deposit  of  calcium  carbonate  in  an 


Fig.  71. — Chronic  interstitial  pancreatitis  of  interacinar  type,  show- 
ing the  invasion  of  an  island  of  Langerhans  by  the  inflammatory  pro- 
cess (Opie). 

organic  matrix,  and  contained  no  appreciable  amount  of 
phosphates,  thus  agreeing  with  the  composition  of  many 
pancreatic  calculi  obtained  from  man.  These  are  often 
found  to  contain  50  per  cent,  or  more  of  calcium  carbonate 
with  traces  of  magnesium,  some  organic  matter,  mainly 
of  a  proteid  nature,  and  of  phosphates  a  varying  amount 
or  none  at  all.     According  to  this  observer,   therefore, 


Pathology  171 

simple  obstruction  of  the  pancreatic  duct  is  sufficient  to 
produce  pancreatic  lithiasis.  Desquamation  of  the  epithe- 
lium of  the  ducts  is  the  primary  effect;  the  cellular  ele- 
ments then  lend  themselves  to  the  formation  of  a  fiVjrillar 
network  which  forms  a  nucleus  for  the  precipitation  of 
calcium  carbonate.  This  salt,  which  is  absent  from  the 
normal  secretion,  appears  as  a  result  of  the  chronic  ir- 
ritation due  to  the  stasis,  which  also  leads  to  a  reac- 
tion in  the  pericanalicular,  interacinar,  and  interlobular 
connective  tissue  of  the  gland.  Thiroloix  has  also  pro- 
duced lithiasis  in  the  pancreas  of  a  dog  experimentally 


» 


Fig.  72. — Pancreas  from  a  case  of  pancreatic  calculi,  laid  open  to 
show  the  calculi  lying  in  the  dilated  duct  of  Wirsung  and  the  attendant 
atrophy  of  the  gland  due  to  the  associated  inflammatory  changes, 
from  a  case  of  diabetes  (Leeds  Museum,  E  E  202). 

by  injecting  a  mixture  of  soot  and  carbolized  liquid 
vaseline  into  the  duct  of  Wirsung,  after  the  duct  of  San- 
torini  had  been  tied.  Post-mortem  the  pancreas  was 
found  to  be  sclerosed,  and  in  the  tail  a  large  cystic  cavity, 
containing  clear,  watery  fluid,  and  surrounded  by  chronic 
inflammatory  tissue,  had  developed.  In  the  cyst,  and 
in  the  duct  also,  small,  hard,  irregular  concretions  had 
formed.  The  view  that  gall-stone  formation  is  due  to 
the  influence  of  micro-organisms  has  been  gaining  ground 
since  Bernheim  directed  attention  to  the  connection 
between  typhoid  fever  and  cholelithiasis  in  1880,  and 
Galippe  found  bacteria  in. the  interior  of  biliary  calculi 


172       The  Pancreas:  Its  Surgery  and  Pathology 


*%>■ 


in  1886.  This  has  naturally  led  some,  and  particularly 
Nimier,  to  attribute  to  micro-organisms  a  causative 
influence  in  the  production  of  pancreatic  calculi.  The 
coexistence  of  biliary  and  pancreatic  calculi  in  a  case 
reported  by  Kinnicutt  was  thought  by  this  observer  to 
point  to  a  common  cause  in  the  shape  of  an  infection 
travelling  up  the  biliary  passages  and  pancreatic  duct. 
Galippe  on  examining  a  stone  found  numerous  bacteria, 

and  Guidicean- 
dra  discovered 
an  organism  very 
similar  to,  if  not 
identical  with, 
bacillus  coli  com- 
munis  in  two 
pancreatic  cal- 
culi. The  con- 
cretions experi- 
mentally pro- 
duced by  Pende 
were,  however, 
sterile,  and  the 
secretion  which 
had  been  re- 
tained in  the 
duct  and  its  tri- 
butaries by  the 
occluding  ligature  gave  no  growth  on  culture. 

Cysts. — ^Experimental  work  on  the  pancreas  has  not 
thrown  much  light  upon  the  etiology  of  the  cysts  occurring 
in  that  organ.  Our  present  knowledge  has  been  obtained 
chiefly  on  the  operating  table  and  at  the  bedside,  and  to 
a  less  extent  in  the  post-mortem  room.  Senn  found  that 
ligature  of  the  pancreatic  ducts  in  animals  caused  only  a 
moderate  dilatation  beyond  the  point  of  constriction,  but 
no  true  cyst  formation.     He  points  out  that  possibly 


^'^S-  73- — Section  of  the  pancreas  shown  in 
Fig.  72,  demonstrating  complete  replacement 
of  the  glandular  parenchyma  by  fibrous  tissue 
(X  50)- 


Pathology 


173 


chronic,  or  intermittent,  obstruction  might  result  in  the 
production  of  cyst,  just  as  ligature  of  a  ureter,  or  acute 
obstruction,  leads  to  atrophy  of  the  kidney,  while  chronic 
obstruction,  or  obstruction  of  an  intermittent  character, 
tends  to  the  development  of  hydronephrosis.  It  is  prob- 
able, therefore,  that  the  simple  so-called  retention  cysts 
of  the  pancreas  do  not  result  solely  from  a  hindrance  to 
the  outflow  of  the  secretion,  but  that  some  other  factor  is 
also  involved.  Heinricus  sug- 
gests that  there  is  some  change 
in  the  pancreatic  juice,  prob- 
ably arising  from  its  admixture 
with  pathological  non-absorb- 
able  products,  and  lessened 
absorptive  power  on  the  part 
of  the  vessels.  The  experiment 
of  Thiroloix,  already  referred 
to,  lends  support  to  the  first 
part  of  the  suggestion,  for  in 
that  instance  a  cyst  of  the 
pancreas  resulted  from  ligature 
of  the  ducts  and  alteration  of 
their  contents  by  the  injection 
of  carbolized  vaseline  and  soot. 
It  will  also  be  remembered  that 
Thiroloix  tied  both  the  duct  of 
Wirsung  and  the  duct  of  San- 
torini.      This   is  an  important 

precaution  to  take,  for  in  some  instances  the  latter  may 
act  as  a  safety-valve  when  the  main  duct  is  obstructed. 
Examination  of  the  pancreas  after  death  in  this  experi- 
ment showed  that  it  was  very  hard  and  deeply  sclerosed 
from  chronic  inflammatory  changes.  Chronic  pancreatitis 
is  also  present  in  many  cases  of  simple  cyst  of  the  pancreas 
in  the  human  subject,  and  there  is  no  doubt,  both  on  ex- 
perimental and  clinical  grounds,  that  it   is   a   frequent, 


•VfFJVff 


Fig.  74. — Pancreas  with 
small  retention  cysts  (Leeds 
Path.  Museum,  E  E  203). 


1 74       The  Pancreas:  Its  Surgery  and  Pathology 

and  probably  the  most  common,  cause  of  the  condition. 
Contraction  of  the  newly  formed  fibrous  tissue  may  cause 
constriction  of  the  ducts  in  places,  while  in  other  parts 
they  may  be  pulled  upon  and  dilated;  the  pancreatic 
secretion  will  then  tend  to  collect  in  the  dilated  portions 
and  undergo  chemical  changes  by  which  its  physical 
characters  are  altered,  and  its  absorption  interfered  with, 
as  Heinricus  suggests. 

Pancreatic  calculi,  as  Thiroloix's  experiment  showed, 
may  originate  under  conditions  similar  to  those  that  give 
rise  to  pancreatic  cysts,  and  both  are  intimately  asso- 
ciated with  chronic  pancreatitis .  It  is  probable ,  therefore , 
that  when  cysts  and  calculi  occur  together,  as  is  sometimes 
the  case,  the  one  is  not  the  cause  of  the  other,  as  is  gener- 
ally assumed,  but  that  both  originate  from  the  same  path- 
ological process.  Blocking  of  the  excretory  duct  by  a 
calculus  is,  however,  likely  to  bring  about  more  rapid 
distension  of  any  cystic  cavity  that  may  be  present  and 
so  increase  its  size  as  to  make  it  clinically  recognisable. 

A  gall-stone  impacted  in  the  ampulla  of  Vater  has  been 
quoted  as  the  cause  of  retention  cysts  of  the  pancreas  in 
some  cases,  and  although  the  blocking  of  the  pancreatic 
duct  in  this  way  may  bring  about  the  distension  of  a 
small  pre-existing  cyst  in  a  similar  manner  to  a  pancreatic 
calculus  in  the  duct  itself,  it  is  not  likely  that  the  obstruc- 
tion is  the  primary  cause  of  the  cyst  formation.  Gall- 
stones and  chronic  pancreatitis  are  very  frequently 
associated,  and  in  some  instances  the  two  conditions  may 
be  due  to  the  same  infective  process,  so  that  in  this  in- 
stance also  the  calculus  is  possibly  but  the  secondary 
cause  that  brings  into  clinical  prominence  cysts  previously 
formed  as  the  result  of  chronic  inflammatory  changes  in 
the  gland. 

Repair  following  traumatism,  duodenal  ulcers,  tumours 
in  the  bile-passages  or  duodenum,  swollen  lymphatic 
glands,  and  even  intestinal  parasites  in  the '  pancreatic 


Pathology 


/o 


duct  are  all  liable  to  be  accompanied  by  chronic  pan- 
creatitis, and  have  each  been  met  with  in  association 
with  cysts  of  the  pancreas.  Whether  they  are  to  be 
regarded  as  the  primary  causes  of  the  cysts,  or  merely 
as  secondary  factors  accentuating  a  pathological  state 
arising  from  the  inflammatory  changes  in  the  gland,  it 
is  difficult  to  say,  but  in  our  opinion  the  latter  is  the  more 
probable  explanation,  at  least  in  many  instances. 

It  has  been  contended  by  some  writers  that  cysts  of 
the  pancreas  may  originate  from  extravasations  of  blood, 
either  within  or  without  the  gland,  and  Hagenbach  has 
distinguished  between  "hsematoma,"  in  which  bleeding 
occurs  into  a  pre-existing  cyst,  and  "apoplectic  cysts," 
resulting  from  haemorrhage  into  softened,  degenerate 
gland-substance.  The  distinction  is,  however,  not  recog- 
nised by  most  modern  authorities,  and  the  presence  of  a 
large  amount  of  blood  in  a  pancreatic  cyst  is  now  gener- 
ally regarded  as  merely  the  result  of  a  more  marked  haem- 
orrhage into  the  cyst  cavity  than  usual. 

Retention  cysts  may  be  single  or  multiple,  unilocular 
or  multilocular.  Two  cysts  of  almost  equal  size  may  be 
present  simultaneously,  or  one  cyst  may  be  found  with  a 
number  of  smaller  ones  attached  to  its  walls.  Obstruc- 
tion of  the  main  duct  near  its  entrance  into  the  duodenum 
may  cause  a  rosary-like  dilatation  to  which  Virchow  has 
given  the  name  of  "ranula  pancreatica."  Dilatation  of 
part  of  the  main  duct  tends  to  give  rise  to  a  spherical  or 
oblong  swelling,  while  obstruction  of  the  smaller  ducts 
may  result  in  the  formation  of  the  collection  of  minute 
cysts  spoken  of  by  Klebs  as  "acne  pancreatica." 

As  a  cyst  enlarges  it  encroaches  upon  and  destroys 
the  substance  of  the  gland,  or,  growing  away  from  the 
pancreas,  it  ma}^  become  pedunculated.  The  size  varies 
within  very  wide  limits,  from  the  tiny  points  of  fluid  met 
with  in  acne  pancreatica,  to  enormous  tumours  holding 
fifteen  or  twenty  litres  of  fluid.     The  wall  of  a  simple 


176       The  Pancreas:  Its  Surgery  and  Pathology 

retention  cyst  is  composed  of  dense  fibrous  tissue,  poor 
in  cells,  and  is  generally  from  3  to  4  mm.  in  thickness. 
The  inner  surface  may  be  smooth,  shining,  and  free  from 
epithelium,  or  be  covered  with  a  layer  of  cylindrical  cells 
resembling  those  lining  the  ducts.  Indications  of  the 
formation  of  the  larger  cysts  by  the  fusion  of  smaller 
cavities  may  be  met  with  in  the  shape  of  projections  of, 
or  septa  on,  the  inner  surface,  and  portions  of  pancreatic 
tissue  are  not  infrequently  found  embedded  in  their  walls. 
The  outer  surface  is  often  traversed  by  large  distended 
blood-vessels. 

The  contents  of  these  cysts  are  of  a  fluid  character, 
but  vary  considerably  in  their  appearance  and  properties. 
The  colour  is  generally  dark  reddish-brown,  but  may  be 
yellow,  greenish,  milky,  or  even  bright  red,  from  recent 
haemorrhage.  The  fluid  is  usually  viscid,  generally 
more  or  less  turbid,  and  of  a  specific  gravity  of  1.007  "to 
1,028.  It  is  generally  alkaline  in  reaction,  is  rarely 
neutral,  and  in  one  instance,  reported  by  Bozeman,  was 
acid.  Albumin,  as  might  be  expected  from  the  very 
frequent  presence  of  blood,  is  a  constant  constituent. 
Sugar  has  been  met  with  in  rare  cases;  2.7  per  cent,  was 
found  in  a  case  of  diabetes  recorded  by  Bull.  In  Hoppe's 
case  the  fluid  contained  0.12  per  cent,  of  urea. 

Microscopical  examination  generally  shows  blood-cells, 
fat,  and  epithelial  cells,  often  cholesterin,  and  rarely 
leucin  and  tyrosin  (Tilger,  Newton  Pitt,  and  Jacobson). 
In  many  of  the  recorded  cases  one  or  more  of  the  pancre- 
atic ferments  have  been  detected,  but  they  have  not  been 
invariably  found,  and  have  indeed  been  proved  to  be 
absent  in  cases  of  undoubted  pancreatic  cyst,  confirmed 
by  post-mortem  examination. 

Proliferation  cysts,  or  cystic  neoplasms,  of  the  pan- 
creas are  very  much  rarer  than  the  form  just  described. 
They  may  be  either  simple  or  malignant,  although  some 
cannot  be  relegated  to   one   or  the  other  category  on 


Pathology  177 

histological  grounds  alone.  The  simple  proliferation 
cyst,  or  "cystadenoma,"  is  usually  multilocular  and  has  a 
lining  of  columnar  epithelium,  which  is  sometimes  seen 
to  dip  down  into  the  wall  of  the  cyst  in  the  form  of  a 
gland,  and  often  covers  polypoid  masses  projecting  into 
the  cavity  of  the  cyst.  The  malignant  form,  or  "cystic 
epithelioma,"  occurs  as  a  series  of  small  cysts,  or  a  poly- 
cystic mass,  showing  patches  of  carcinomatous  material 
in  the  walls.  The  cells  of  the  solid  portions  of  growth 
are  arranged  in  irregular  groujjs,  devoid  of  any  true 
glandular  order,  and  are  large  polyhedral  and  often 
multinuclear.  In  Hartmann's  case  the  tumour  is  re- 
ported to  have  contained  200  grams  of  chocolate-coloured 
fluid.  Metastatic  deposits  may  be  found  in  the  liver, 
pancreatic  glands,  duodenum,  and  in  other  situations. 
The  formation  of  cysts  in  cancer  of  the  pancreas  has  been 
described  by  Roux. 

It  has  been  suggested  that  tumours  arising  in  the 
neighbourhood  of  the  pancreas,  and  closely  resembling 
multilocular  proliferation  cysts  of  that  organ,  may  arise 
from  remnants  of  the  Wolffian  body  and  be  mistaken  at 
operation  for  pancreatic  growths.  Alonprofit  has  pub- 
lished a  case  in  which  a  large  cystic  tumour  was  so  firmly 
attached  to  the  spleen  and  the  tail  of  the  pancreas  that 
it  was  necessary  to  remove  both  to  complete  the  opera- 
tion. From  the  microscopical  characters  and  situation 
of  the  growth  it  was  concluded  that  it  had  originated  from 
remains  of  the  Wolffian  body  in  the  posterior  layer  of  the 
mesocolon.  Dunning  has  also  reported  a  somewhat 
similar  case.  Invasion  of  the  substance  of  the  pancreas 
by  such  growths,  or  by  similar  neoplasms  in  the  left 
suprarenal  capsule,  may  readily  be  mistaken  at  operation 
for  a  growth  of  the  pancreas,  and  the  presence  of  adhe- 
rent remains  of  the  pancreatic  tissue  may  tend  to  confirm 
the  error  on  microscopical  examination. 

Hydatid  cyst  and  congenital  cystic  disease  of  the  pan- 


1 78       The  Pancreas:  Its  Surgery  and  Pathology 

creas  are  both  exceedingly  rare.  They  differ  in  no  essen- 
tial particular  from  similar  lesions  met  with  in  the  liver, 
kidneys,  and  elsewhere. 

Pseudo-cysts,  as  Korte  has  proposed  to  call  them, 
constitute  a  large  proportion  of  the  cases  reported  as 
pancreatic  cysts.  They  are  fluid  tumours  found  in  more 
or  less  close  proximity  to  the  pancreas,  but  not  originating 


Liver 


Pancreas 


Lesser  peritoneal 
sac 


Stomach 


Colon 


Small  intestine 


Fig.  75. — Diagram  to  show  the  method  of  origin  of  a  pseudo-cyst  of  the 

pancreas. 


in  the  substance  of  the  gland.  The  most  frequent  form  is 
that  described  by  Jordon  Lloyd,  in  which  an  efliusion  takes 
place  into  the  lesser  peritoneal  cavity,  mainly  as  the  result 
of  injury  of  the  pancreas.  The  escape  of  blood,  followed 
by  pancreatic  juice,  into  the  lesser  cavity  of  the  perito- 
neum sets  up  a  mild  form  of  peritonitis  which  may  close 
the  foramen  of  Winslow  and  produce  a  tumour,  which, 


Pathology  179 

during  life,  it  is  impossible  to  distinguish  from  a  true 
pancreatic  cyst.  The  fact  that  a  cavity  within  the  ab- 
domen contains  a  fluid  possessing  digestive  powers  is 
no  proof  that  it  is  a  retention  cyst,  but  merely  that 
it  is  probably  connected  with  the  pancreas.  Other 
forms  of  pseudo-cyst  will  be  considered  in  connection 
with  the  diagnosis  of  swellings  of  the  pancreas,  but  it 
may  be  mentioned  here  that  the  greater  proportion  are  met 
with  in  males,  who  are  more  exposed  to  injury,  whereas 
the  majority  of  true  cysts  appear  to  occur  in  women. 

The  relation  of  trauma  to  cysts  of  the  pancreas  has 
been  debated  by  Korte,  Tilger,  Moynihan,  and  others. 
Korte  has  described  two  classes  of  traumatic  cysts  of 
the  pancreas,  one  in  which,  after  long-continued  discom- 
fort in  the  epigastrium,  a  tumour  gradually  develops, 
and  the  other  where,  within  a  short  time  of  the  injury,  a 
tumour  of  considerable  size  has  formed.  In  the  former 
it  is  possible  that  the  injury  leads  to  a  chronic  interstitial 
inflammation,  such  as  is  known  to  follow  experimental 
injury  of  the  pancreas  in  dogs,  and  that  this  gradually 
gives  rise  to  cyst-formation  in  the  manner  already  des- 
cribed. In  the  latter  class  of  cases,  where  the  tumour 
forms  rapidly,  and  increasing  up  to  a  certain  point,  then 
remains  stationary,  the  effusion  is  probably  poured  out 
into  a  pre-existing  cavity,  such  as  the  omental  bursa, 
and  is  a  form  of  pseudo-cyst. 

Tumours. — The  solid  tumours  met  with  in  the  pancreas 
are  carcinoma,  sarcoma,  adenoma,  and  lymphoma.  It 
was  formerly  taught  that  carcinoma  is  the  most  frequent 
of  all  diseases  of  the  pancreas,  and  although  it  is  the  most 
common  new  growth,  it  is  certainly  not  the  commonest 
lesion.  The  mistake  has  arisen  from  too  great  reliance 
being  placed  upon  naked-eye  observation  in  the  post- 
mortem room,  and  the  failure  of  surgeons  in  the  past  to 
recognize  that  many  swellings  of  the  head  of  the  pancreas 
associated  with  jaundice  are  merely  inflammatory.     The 


i8o       The  Pancreas:  Its  Surgery  and  Pathology 


importance  of  the  latter  point  was  strongly  insisted  upon 
by  one  of  us  in  1900,  and  has  since  been  confirmed  by  a 
number  of  independent  observers. 


Fig.  76. — Spheroidal- 
celled  carcinoma  of  the  pan- 
creas (X  50). 


^ 


Fig.     77.  —  Columnar -celled 
carcinoma      of      the      pancreas 

(X  50). 


Fig.  78. — Columnar-celled 
carcinoma  of  the  pancreas 
(X   150). 


*^*^^^ 


Fig.  79.  —  Columnar  -  celled 
carcinoma  of  the  pancreas  under- 
going colloid  change,  from  a  case 
of  diabetes  (X  40). 


Primary  carcinoma  of  the  pancreas  may  begin  in  the 
glandular  epithelium,  or  in  the  cells  lining  the  excretory 


Pathology 


i»i 


ducts.  In  the  former  case  it  is  of  the  spheroidal,  and  in 
the  latter  is  generally  said  to  be  of  the  columnar,  ty^je. 
Letulle,  however,  maintains  that  primary  carcinoma  of 
the  duct  of  Wirsung  is  spheroidal  and  not  columnar 
celled.  Spheroidal-celled  carcinoma  is,  at  any  rate,  -much 
the  more  common,  and  is  usually  of  the  scirrhous  variety. 
Encephaloid  tumours  are  sometimes  met  with,  and  rarely 
a  colloid  carcinoma,  resulting  from  degenerative  changes 
in  a  columnar-celled  growth,  has  been  encountered. 
Hillier  and  Goodall  have  distin- 
guished a  variety  of  carcinoma 
characterised  by  great  irregu- 
larity in  the  size  and  shape  of  the 
cells,  which  they  believe  arises 
in  the  island  of  Langerhans. 

The  most  frequent  site  of  the 
lesion  is  in  the  head  of  the  gland, 
some  62  per  cent,  of  the  recorded 
cases  being  in  that  position.  In 
about  5.5  per  cent,  the  tail  of 
the  organ  was  most  affected,  in 
3.5  per  cent,  the  body,  and  in 
29  per  cent,  there  was  a  diffuse 
growth  involving,  more  or  less, 
the  whole  of  the  pancreas.  The 
duct  of  Wirsung  is  compressed 

by  the  growth  in  nearly  all  instances.  Courvoisier  found 
it  obliterated  in  55  out  of  66  cases,  and,  according  to 
Boldt,  it  is  dilated  beyond  the  point  of  stricture  in 
one-third  of  all  cases  of  malignant  disease  of  the  head 
of  the  gland.  Growth  in  this  situation  almost  always 
causes  gradually  increasing,  painless  jaundice  with  en- 
largement of  the  gall-bladder,  points  of  some  importance 
in  the  diagnosis  of  the  condition  from  obstruction  of  the 
duct  due  to  gall-stones,  in  which,  although  there  may 
be  equally  deep  jaundice,  there  is  commonly  a  history  of 


Fig.  80. — Cancer  of  the 
head  of  the  pancreas  (St. 
George's  Hospital  Museum, 
201  B). 


1 82       The  Pancreas:  Its  Surgery  and  Pathology 

pain   and  the  gall-bladder  is  small  and  shrunken.     The 


Fig.  8 1 . — Cancer  of  the  head  of  the  pancreas  showing  dilatation  of  the 
duct  of  Wirsung  (St.  Thomas'  Hosp.  Museum,  1415). 


Fig.  82. — Carcinoma  of  the  body  of  the  pancreas  (Royal  Coll.  of  Surg. 
Museum,  3835). 

explanation    of    the    different    behaviour    of    the    gall- 
bladder in   the  two   conditions   appears  to  be  that,  as 


Pathology 


183 


the  result  of  gall-stone  irritation,  it  frequently  becomes 
diminished  in  size  and  adherent,  so  that  when  the 
common  duct  is  subsequently  blocked,  it  is  unable  to 
expand,  whereas  blocking  of  the  duct  by  a  tumour  at 
once  causes  distension  of  the  gall-bladdet,  for  it  has  not 
been  altered  by  previous  inflammatory  changes.  It  has 
also  to  be  remembered  that, 
although  the  obstruction  due 
to  a  large  gall-stone  may  pos- 
sibly be  absolute  at  first,  it 
quickly  ceases  to  be  so,  and 
small  quantities  of  bile  find 
their  way  into  the  intestine, 
but  that  in  malignant  disease 
of  the  head  of  the  pancreas 
the  obstruction  gradually  in- 
creases, and  eventually  be- 
comes absolute,  so  that  not 
a  trace  of  stercobilin  can  be 
found  in  the  faeces.  The 
backward  pressure  in  the 
ducts  in  these  cases,  while  it 
prevents  the  excretion  of  bile, 
does  not  interfere  with  its 
formation,  and  it  is  conse- 
quently absorbed  by  the 
lymphatics  and  gives  rise  to 
jaundice.  The  pressure  in 
the  ducts  also  prevents  the 
bile  reaching  the  gall-bladder 

and  it  is  consequently  found  to  be  only  filled  with  mucus. 
The  relations  and  size  of  some  of  these  growths  explain, 
the  compression  and  perforation  of  the  duodenum,  stom- 
ach, colon,  ureter,  portal  vein,  aorta,  vena  cava,  splenic 
artery  and  vein,  and  superior  mesenteric  vein  that  some- 
times take  place. 


Fig.  83. — Cancer  of  the 
head  of  the  pancreas  producing 
dilatation  of  the  common  bile- 
duct  and  gall-bladder  (Univ. 
Coll.  Hosp.  Museum,  3198). 


184       The  Pancreas:  Its  Surgery  and  Pathology 


Secondary  deposits  occur  most  frequently  in  the  liver, 
but  may  be  found  anywhere,  or  indeed  everywhere,  for 
Oser  has  reported  general  carcinomatosis  from  a  pancrea- 
tic growth,  although  the  primary  origin  of  the  growth  is 
perhaps  rather  a  matter  of  surmise  in  such  cases.  As  in 
carcinoma  elsewhere,  carcinoma  of  the  pancreas  is  most 
frequent  after  the  fortieth  year.  Bohn  has,  however, 
reported  the  occurrence  of  the  disease  in  a  child  of  seven 
months,  Kuhn  in  one  of  two  years,  and  Dutil  in  a  patient 
fourteen  years  of  age. 

In  many  cases  of  primary  carcinoma  there  is  a  coexist- 
ing fibrosis  of  the  gland, 
and,  although  it  is  prob- 
able that  in  many  in- 
stances the  overgrowth 
of  fibrous  tissue  results 
from  the  inflammatory 
changes  set  up  by  the 
spread  of  the  tumour, 
it  is  possible  that,  in 
some,  the  fibrosis  may 
have  been  the  primary 
condition,  and  that  the 
carcinoma  may  have 
originated  in  groups  of 
cells  isolated  by  the 
fibrous  tissue,  in  much  the  same  way  as  primary  cancer 
of  the  liver  appears  to  arise  from  groups  of  cells  similarly 
isolated  in  cirrhosis  of  that  organ.  The  frequent  asso- 
ciation of  chronic  pancreatitis  with  cholelithiasis  has 
already  been  insisted  upon,  and  it  is  not  unlikely  that  gall- 
stone trouble  may  thus  be  a  cause  of  cancer  of  the  pan- 
creas. The  very  high  proportion  of  cases  in  which  the 
primary  growth  is  situated  in  the  head  of  the  gland 
tends  to  favour  the  view  that  there  may  be  some  such 
association. 


Fig.  84. — Colloid  carcinoma  of  the 
pancreas  (St.  George's  Hosp.  Museum, 
201  D). 


Pathology 


185 


Primary  sarcoma  is  very  rare.  Segre  met  with  only 
two  cases  in  11,492  post-mortems,  anr]  Hale  White  men- 
tions only  one,  of  undoubted  primary  sarcoma,  in  6708 
autopsies  at  Guy's  Hospital.  In  most  instances,  where  a 
histological  examination  has  been  made,  the  growth  has 
been  described  as  a  small  round-celled  sarcoma  or  a 
lymphosarcoma,  but  it  is  doubtful  whether  some  of  these 
can  be  regarded  as  truly  primary  growths  of  the  pancreas, 
for  although  the  pancreas  was  deeply  involved,  the 
lymphatic  glands,  duodenum,  or 
other  structures  have  also  been 
affected.  A  very  large  spindle- 
celled  sarcoma  of  the  pancreas  is 
preserved  in  University  College 
Hospital  Museum  (No.  3200), 
and  mixed-celled  sarcomas  have 
been  described  by  Healey  and 
by  Kakels.  The  pancreatic  tu- 
mour in  the  former  case  con- 
sisted chiefly  of  round  cells,  but 
in  some  parts  groups  of  mixed 
cells  were  seen,  while  the  sec- 
ondary growths,  which  were 
present  in  the  liver,  were  chiefly 
of  the  large  spindle-celled  vari- 
ety. Kakels'  case  was  a  very 
vascular  mixed-celled  sarcoma  in  the  tail  of  the  gland, 
and,  according  to  him,  is  only  the  third  authentic  case 
of  a  primary  sarcoma  in  that  situation.  Kronlein  and 
Lubarsch  have  each  reported  a  case  of  angiosarcoma.  A 
sarcoma  of  the  pancreas,  in  which  typical  epithelial  pro- 
liferations were  found  in  the  growing  parts,  has  been 
described  by  Michelsohn,  and  a  similar  case  of  "sarco- 
carcinoma"  has  been  reported  by  Baudach.  Briggs  re- 
moved an  old  hydatid  cyst  from  the  pancreas  of  a  woman 
the  walls  of  which,  on  microscopical  examination,  were 


Fig.  85. — Sarcoma  of 
the  pancreas  (St.  George's 
Hospital  Museum,  201  E). 


i86       The  Pancreas:  Its  Surgery  and  Pathology 

found  to  have  undergone  sarcomatous  degeneration.  This 
case  is  of  some  pathological  interest  in  view  of  the  recent 
observations  of  Borrel  on  the  supposed  relation  of  can- 
cerous tumours  to  helminthiasis. 

The  pancreas  is  said  by  Oser  to  be  the  seat  of  secondary 
deposits  in  more  than  lo  per  cent,  of  all  cases  of  primary 
carcinoma  of  the  stomach,  and,  as  metastasis  also  takes 
place  from  organs  elsewhere,  such  as  the  rectum,  sigmoid 
flexure,  oesophagus,  ovary,  and  breast,  it  is  not  uncommon. 
The  majority  of  authors  state  that  secondary  carcinoma 
is  more  frequently  met  with  than  primary  growth,  but 
Hale  White  found  only  twenty-four  cases  with  secondary 
deposits,  as  against  thirty-one  with  a  primary  growth, 
in  the  Guy's  Hospital  post-mortem  records  from  1884  to 
1897.  Hale  White,  from  an  analysis  of  these  records, 
confirms  the  statement  of  Lancereaux  that  the  stomach 
is  the  organ  from  which  the  growth  most  frequently 
extends  directly  to  the  pancreas.  Olivier  and  Dieckhoff 
are  disposed  to  doubt  some  cases  described  as  primary 
pancreatic,  and  think  that  their  microscopical  characters 
suggest  that  they  may  have  really  originated  in  the  glands 
of  the  duodenum.  Orth,  however,  points  out  that  the 
transition  of  the  atypical  growth  of  intestinal  gland  acini 
into  cancerous  alveoli  is  not  always  easy  to  establish  in 
primary  tumours,  and  that  columnar-celled  carcinoma 
may  originate  in  excretory  ducts  of  the  pancreas  as  well 
as  in  the  duodenal  glands.  Secondary  deposits  of  carci- 
noma may  be  found  in  any  part  of  the  gland,  but  whenever 
present  in  the  pancreas  are  also  to  be  found  at  the  same 
time  in  many  other  organs  of  the  body. 

Secondary  sarcoma  of  the  pancreas  is  not  uncommon. 
It  occurs  most  frequently  as  a  lymphosarcoma  arising 
from  the  abdominal  lymph  glands,  mediastinum,  or 
duodenum.  A  number  of  cases  of  melanotic  sarcoma 
have  also  been  described.  In  these  the  primary  growth 
is  most  commonly  situated  in  the  eye. 


Pathology 


187 


Adenoma  of  the  pancreas  may  originate  from  the  duct- 
epitheHum,  the  gland  acini,  the  islands  of  Langerhans,  or 
from  suprarenal  rests.  Examples  of  this  condition  have 
been  described  by  Thierfelder,  Biondi,  Cesaris-Demel, 
Neve,  and  Nicholls,  but  in  at  least  one  of  them  the  diag- 
nosis is  open  to  question.  Thierfelder's  case  was  a  man 
who  died  of  general  tuberculosis ;  a  definitely  encapsuled 
but  easily  shelled-out  tumour  was  found  in  the  head  of 
the  pancreas.  Biondi  excised  a  "  fibro-adenoma"  from 
the  head  of  the  gland.  Cesaris-Demel 
found  a  growth,  the  structure  of 
which  was  similar  to  that  of  the  pan- 
creas, but  its  interstitial  tissue,  as 
well  as  that  of  the  gland  substance, 
was  thickened.  He  suggests  that  the 
cirrhosis  of  the  pancreas,  developed 
upon  a  syphilitic  basis,  incited  the 
formation  of  the  tumour.  Neve  de- 
scribes a  case  in  which  there  was  a 
glandular  tumour  in  the  region  of  the 
pancreas  adherent  to  the  duodenum 
and  compressing  the  common  duct. 
In  Nicholls'  case  a  small,  encapsuled, 
round,  somewhat  flattened  nodule 
was  present  on  the  anterior  surface 
of  the  pancreas  which,  on  microscop- 
ical examination,  was  found  to  con- 
sist of  a  stroma  of  connective  tissue, 
arranged  in  the  form  of  imperfect  and  irregular  alveoli, 
that  contained  cells  of  a  glandular  type  forming  masses 
and  wavy  bands.  As  compared  with  the  acinous  cells, 
those  of  the  tumour  were  smaller,  their  nuclei  were  rela- 
tively larger,  and  their  cytoplasm  was  looser  in  texture  and 
stained  more  faintly  and  irregularly.  Nicholls  concluded, 
from  its  staining  reactions  and  structure,  that  the  start- 
ing-point of  the  tumour  was  in  an  island  of  Langerhans. 


Fig.  86. — Deposits 
of  melanotic  sarcoma 
in  the  pancreas  with 
haemorrhage  into  the 
gland  and  fat  necrosis 
(St.  Thomas'  Hospi- 
tal Museum,  14 16). 


1 88       The  Pancreas:  Its  Surgery  and  Pathology 

Lymphadenoma  of  the  pancreas  is  excessively  rare; 
but  two  cases  are  referred  to  by  Lancereaux,  and  Hale 
White  speaks  of  the  condition  as  having  been  met  with 
at  Guy's  Hospital  once  in  fourteen  years,  in  a  patient 
who  died  from  Hodgkin's  disease. 


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CHAPTER  IX 

FAT  NECROSIS 

The  term  "fat-tissue  necrosis"  was  introduced  by 
Langerhans  to  describe  the  small,  opaque,  yellowish- 
white  areas  described  by  Balser  as  occurring  in  the  inter- 


Fig.  87. — ^Areas  of  fat  necrosis  in  the  mesenteric  and  omental  fat 
and  in  the  abdominal  wall  in  a  case  of  acute  hsemorrhagfic  pancreatitis 
(Fison). 

acinous  tissue  of  the  pancreas,  and  more  rarely  in  the 
surrounding  fat,  of  many  bodies  taken  indiscriminately 
in  the  post-mortem  room.  Balser  had  observed  the 
lesion  in  five  out  of  twenty-five  bodies  he  examined,  and 

190 


Fat  Necrosis 


191 


in  two  found  that  the  process  not  only  involved  the  fat 
about  the  pancreas,  but  was  also  present  in  scattered  foci 
at  a  considerable  distance  from  the  gland.  He  believed 
that  occasionally  the  areas  might  become  confluent  and 
cause  death,  either  by  their  extent  and  the  simultaneous 
sequestration  of  large  portions  of  the  abdominal  fat,  or 
from  haemorrhage,  indications  of  which  he  found  in  the 
adjacent  tissue,  especially  when  the  changes  were  exten- 
sive. Balser  made  microscopical  preparations  from  the 
affected  areas  and  adjacent 
tissues,  and  came  to  the  con- 
clusion that  the  lesion  was  due 
to  an  increase  of  the  fat  cells. 
Chiari  confirmed  the  observa- 
tions of  Balser  as  to  the  oc- 
currence of  the  condition,  and 
stated  that  he  had  found  it 
in  five  cases  of  severe  disease 
of  the  pancreas,  but  did  not 
agree  as  to  its  nature,  for  in 
his  opinion  the  lesion  was 
due  to  fatty  degeneration  and 
simple  necrosis. 

A  correct  explanation  of 
the  essential  nature  of  the 
process  was  first  afforded  by 
the  chemical  and  histological 
studies  of  Langerhans,  who  showed  that  the  change  of 
the  fat  cells  into  granular  balls,  and  the  appearance  in  the 
older  foci  of  peculiar  flakes  of  the  size  and  form  of  ordi- 
nary fat  cells,  observed  by  Chiari,  are  due  to  splitting  of 
the  neutral  fat  of  the  cells  into  fatty  acid  and  glycerine. 
The  fatty  acids  are  deposited  as  needle-like  crystals 
within  the  cells,  which  have  lost  their  nuclei  and  are 
necrotic,  while  the  soluble  glycerine  is  absorbed.  Subse- 
quently union  of  the  fatty  acids  with  calcium  gives  rise 


Fig.  88.  — Portion  of  the 
omental  fat  from  the  same  case 
of  acute  pancreatitis,  showing 
areas  of  fat  necrosis  (Fison). 


192       The  Pancreas:  Its  Surgery  and  Pathology 

to  irregular  and  often  globular  masses  of  lime  salts,  which 
more  or  less  preserve  the  outlines  of  the  cells.  Langerhans 
found  that  an  entire  lobule,  or  several  neighbouring 
lobules,  may  form  a  dead  mass  which  is  separated  from 
the  living  tissue  by  a  proliferation  of  the  fixed  tissue  cells, 
and  that  the  dissecting  inflammation  is  most  conspicuous 


.'  >.v-'  -' 


" '  >« 


,'/' 


,  'I.. 


■  <r 


»-•   *V.  *,"     "'"J.*^  '  '"      '■  . 


.K    ■. 


Fig.  89. — Microphotograph  of  fat  necrosis  of  the  body  of  the  pan- 
creas in  a  case  of  carcinoma  of  the  head  of  the  gland.  General  view 
showing  normal  islands  of  Langerhans,  and  a  spot  of  fat  necrosis  in  the 
centre  alongside  a  bifurcating  vessel  (X  130)  (Scott). 

in  the  neighbourhood  of  the  strands  of  connective  tissue, 
although  the  zone  of  reaction  is  often  not  complete  and 
necrotic  cells  are  found  in  contact  with  those  that  are  still 
unchanged. 

Numerous  instances  of  multiple  fat  necrosis  have  been 
recorded   since   the   earlier   observations   of    Balser   and 


Fat  Necrosis 


193 


/  " 


/, 


<:^ 


•  ## 


Fig.  90. — Microphotograph  of  fat  necrosis  of  the  body  of  the  pan- 
creas in  a  case  of  carcinoma  of  the  head  of  the  gland.  The  same  spot 
of  fat  necrosis  (X  264)  (Scott). 


Fig.  91. — Microphotograph  of  fat  necrosis  of  the  body  of  the  pan- 
creas in  a  case  of  carcinoma  of  the  head  of  the  gland.  Crystalline  ap- 
pearance in  a  spot  of  fat  necrosis  ( X  200)  (Scott). 

13 


194       The  Pancreas:  Its  Surgery  and  Pathology 


Chiari,  associated,  as  a  rule,  with  well-marked  structural 
changes  in  the  pancreas.  The  lesion  is  usually  limited 
to  the  fat  of  the  abdomen,  and  is  most  extensive  in  the 
neighbourhood  of  the  pancreas,  but  may  extend  to  the 
subpleural  fat,  or  even  to  the  subcutaneous  tissue.  Foci 
of  fat  necrosis  in  the  last  situation,  corresponding  to 
reddish  areas  in  the  skin  during  life,  have  been  observed 
by  Hansemann  in  two  cases.  The  con- 
dition is  not  confined  to  man,  but  has 
been  found  in  domestic  animals  by 
Balser,  Williams,  Alt,  Heller,  and  others. 
The  opaque,  dull -white,  or  yellowish- 
white  areas,  often  surrounded  by  a  nar- 
row haemorrhagic  zone,  seen  in  multiple 
or  disseminated  fat  necrosis  are  in  strik- 
ing contrast  to  the  clear  yellow  of  the 
surrounding  normal  fat,  and  are,  as  a 
rule,  sufficiently  characteristic.  They 
may  be  differentiated  still  further  by 
the  application  of  a  half-saturated  solu- 
tion of  acetate  of  copper,  as  suggested 
by  Bender,  when  the  affected  parts  turn 
green  (Fig.  92).  Small  areas  of  necrosis 
not  visible  to  the  naked  eye  may  also 
be  demonstrated  by  this  means.  The 
areas  are  of  firmer  consistency  than  the 
tissues  in  which  they  are  situated,  and 
hence  can  be  felt  on  passing  the  finger 
over  the  surface.  They  do  not,  as  a 
rule,  however,  project  like  miliary  tu- 
bercles. In  the  neighbourhood  of  the  pancreas  they 
may  be  confluent,  but  elsewhere,  although  they  may 
be  thickly  scattered,  are  usually  seen  as  distinct  oval  or 
round  patches,  several  millimetres  in  diameter,  which  in 
section  have  the  shape  of  a  split  pea  with  the  flat  surface 
toward  the  peritoneum.     Para-pancreatic  foci,  limited  to 


Fig.  92." — Sec- 
tion of  the  body 
of  the  pancreas  in 
a  case  of  carcino- 
ma of  the  head  of 
the  gland  treated 
with  Benda's  so- 
lution, showing 
areas  of  fat  ne- 
crosis (stained 
green),  the  dilated 
duct  of  Wirsung 
in  the  centre,  and 
the  splenic  artery 
above  (Leeds 
Path.  Museum, 
EE204X). 


Fat  Necrosis  195 

the  fat  within  or  upon  the  pancreas,  are  usually  small  and 
are  easily  overlooked.  Although  they  are  not  so  common 
as  Balser's  observations  would  suggest,  they  are  not  in- 
frequently met  with  when  carefully  sought  for. 

The  association  of  fat  necrosis  with  lesions  of  the  pan- 
creas, and  the  greater  severity  of  the  changes  in  the 
neighbourhood  of  the  gland,  early  suggested  that  the 
two  were  in  some  way  connected.  Balser,  Langerhans, 
Seitz  and  Fraenkel  considered  that  fat  necrosis  was  the 
cause  of  the  inflammation,  haemorrhage,  and  necrosis  of 
the  pancreas  with  which  it  often  occurred.  Ponfick 
thought  that  it  merely  predisposed  the  tissues  to  in- 
flammatory and  other  changes.  Dieckhoff  believed 
that,  although  fat  necrosis  may  give  rise  to  diseases  of  an 
inflammatory  nature,  it  is  possible  that  the  same  cause 
which  occasions  the  inflammation  may  also  cause  fat 
necrosis.  Lindsay  Steven  admitted  that  extensive  fat 
necrosis  might  lead  to  necrosis  of  the  pancreas,  but 
considered  that  the  two  processes  were  usually  indepen- 
dent. Fitz,  and  subsequently  Korte,  maintained,  how- 
ever, that  fat  necrosis  was  the  result  of  pathological  pro- 
cesses affecting  the  pancreas,  and  this  is  the  explanation 
that  is  now  generally  accepted. 

Some  observers,  including  Balser,  have  sought  to  con- 
nect fat  necrosis  with  a  bacterial  invasion,  and  have 
succeeded  in  finding  a  variety  of  micro-organisms  in  the 
affected  parts.  Jackson  and  Ernst,  in  a  case  of  suppura- 
tive pancreatitis  with  fat  necrosis  reported  by  Fitz, 
isolated  four  different  types  of  bacteria.  Ponfick  culti- 
vated a  bacillus  which  he  thought  was  allied  to  bacillus 
coli  communis,  and  Welch  also  identified  bacillus  coli 
in  a  case  of  hsemorrhagic  pancreatitis  with  fat  necrosis. 
Other  investigators  have  obtained  similar  results,  but 
Fraenkel,  on  the  other  hand,  in  spite  of  most  careful 
microscopical  and  cultural  investigations,  was  unable  to 
find  any  evidence  of  bacterial  infection.     More  recently 


196       The  Pancreas:  Its  Surgery  and  Pathology 

Sawyer  has  made  cultures  from  the  necrotic  patches  in  a 
case  of  fat  necrosis  and  found  that  they  were  sterile, 
and  microscopical  sections  in  other  cases  also  failed  to 
shew  any  micro-organisms.  The  explanation  of  the 
discordant  results  obtained  by  different  observers  is  no 
doubt  that  offered  by  Hlava,  Fitz,  Leonhard,  and  Welch, 
who  consider  that  the  presence  of  micro-organisms  is 
due  to  a  secondary  invasion  and  takes  no  part  in  the 
production  of  the  lesion. 

Experimental  work  on  the  production  of  fat  necrosis 
was  first  undertaken  by  Langerhans.  He  injected  an 
infusion,  made  by  grinding  up  the  pancreas  of  a  freshly 
killed  rabbit  with  finely  splintered  glass,  into  rabbits  and 
dogs,  and  succeeded,  in  one  of  thirteen  experiments,  in 
producing  a  small  opaque  focus  at  the  site  of  injection, 
which  had  the  histological  characters  of  fat  necrosis.  He 
consequently  concluded  that  it  was  possible  to  produce 
fat  necrosis  by  the  action  of  fresh  pancreatic  juice  upon 
living  fat  tissue.  Jung  attempted  to  reproduce  the  con- 
dition by  introducing  gelatin  capsules  containing  pan- 
creatic extracts,  and  pieces  of  fresh  pancreas  from  another 
animal,  into  the  abdominal  cavities  of  rabbits.  Three 
experiments  gave  doubtful  results,  as  peritonitis  followed, 
but  well-marked  areas  of  fat  necrosis  were  produced  in 
one  instance.  Under  the  direction  of  Hildebrand,  a 
series  of  investigations  were  undertaken  by  Dettmer. 
Fat  necrosis  about  the  distal  portion  of  the  pancreas  was 
found  to  be  produced  by  constricting  it  with  a  ligature, 
and  was  more  abundant  when  the  veins  of  the  ligatured 
part  were  tied  to  prevent  possible  absorption  by  the 
blood-vessels  of  the  obstructed  secretion.  Similar  lesions 
in  the  neighbourhood  of  the  gland  were  also  produced 
by  cutting  it  across  transversely  and  allowing  the  pancrea- 
tic juice  to  flow  directly  into  the  abdominal  cavity. 
Injections  of  trypsin  gave  rise  to  no  fat  necrosis,  so  that 
it  was  probable  that  the  condition  was  not  due  to  the 


Fat  Necrosis  i97 

proteolytic  but  to  the  fat-splitting  ferment  of  the  pan- 
creatic juice.     Korte  obtained  similar  experimental  results 
and  concluded  that  fat-tissue  necrosis  may  be  produced 
experimentally  by  injuries  and  inflammations  of  the  gland, 
especially  by  solution  of  continuity  and  the  implantation 
of  excised  pieces.     The  experiments  of  Flexner,  Williams, 
and  Milisch,  conducted  on  lines  similar  to  those  of  Dett- 
mar  and   Hildebrand,  also   confirmed   the   observations 
made  by  those  investigators.     Oser  produced  foci  of  fat 
necrosis  about  the  pancreas,  and  in  the  omentum,  by 
ligaturing  all  the  blood-vessels  of  the  organ  and  separating 
it  from  the  duodenum,  thus  entirely  depriving  it  of  its 
blood  supply.      Hasmorrhagic  infiltration  of  the   paren- 
chyma, and  fat  necrosis  in  the  neighbourhood  of  injured 
tissue,  were  found  by   Blume  to  result  from  complete 
obstruction  of  the  circulation  of  a  portion  of  the  gland 
for  so  short  a  time  as  twenty  minutes.     As  the  result 
of  a  large  number  of  experiments  in  which  they  ligatured 
the  pancreas,  and  tied  or  cut  the  ducts,  Katz  and  Wink- 
ler came  to  the  conclusion  that  fat  necrosis  is  produced 
by  the  fat-splitting  ferment  of  the  pancreatic  juice,  but 
that  its  activity  is  particularly  developed  in  those  situa- 
tions where  the  resistance  of  the  parts  has  been  lowered 
by  obstruction  of  the  circulation  or  infiltration  with  blood. 
In  most  of  the  experiments  already  referred  to  the 
production  of  fat  necrosis  had  been  confined  to  the  ab- 
dominal fat,  and  usually  to  that  in  the  immediate  neigh- 
bourhood of  the  pancreas.     Opie,  however,  in  a  series  of 
experiments  he  undertook  succeeded  in  reproducing  the 
more  widely  spread  condition  occasionally  observed  in 
man,  and  showed  that  the  same  cause  is  responsible  for  it 
as  for  the  local  lesions.     He  found,  as  previous  observers 
had  done,  that  ligature  of  the  pancreatic  ducts  does  not 
always  give  rise  to  fat  necrosis,  even  when  the  animal 
survives  the  operation  for  three  weeks  or  more,  but  in  six 
experiments    he    succeeded    in    bringing    about    changes 


198       The  Pancreas:  Its  Surgery  and  Pathology 

which  in  two  instances  extended  to  the  subcutaneous 
and  pericardial  fat,  besides  involving  that  of  the  abdomen, 
and  in  other  four  affected  the  omental  and  mesenteric  fat. 
The  extent  and  intensity  of  the  lesion  appeared  to  depend 


Fig.  93. — Experimental  fat  necrosis:  Administration  of  pilocarpin 
after  ligation  of  pancreatic  ducts.  Foci  of  necrosis  in  omental  and 
mesenteric  fat,  in  fat  below  parietal  peritoneum,  and  in  fat  of  parietal 
pericardium  (Opie). 

Upon  the  time  the  animal  survived  the  operation  of 
ligating,  or  tying  and  cutting,  the  pancreatic  ducts,  for 
when  death  took  place  in  twenty  to  twenty-five  days 
the  necrosis  was  more  extensive  than  when  the  animal 
lived  a  shorter  time.     Opie  assumed  that  this  might  be 


Fat  Necrosis  199 

due  to  the  condition  being  produced  by  a  gradual  diffu- 
sion of  the  pancreatic  juice,  and  that,  if  the  activity  of  the 
gland  could  be  stimulated,  fat  necrosis  in  distant  parts 
would  more  readily  take  place.  Making  use  of  the  ob- 
servation of  Heidenhain,  Gottlieb,  and  others  that  the 
pancreatic  secretion  is  increased  by  pilocarpin,  he  ad- 
ministered that  drug  to  a  cat,  after  tying  the  pancreatic 
ducts,  and,  at  the  end  of  four  days,  found  that  there  was 
local  necrosis  of  the  omental,  mesenteric,  retroperitoneal, 
intermuscular,  and  pericardial  fat,  whereas  in  a  control 
animal,  to  which  no  pilocarpin  had  been  given,  there 
were,  in  the  same  time,  only  small  foci  of  necrosis  in  the 
neighbourhood  of  the  pancreas. 

Milisch,  as  the  result  of  his  experiments,  came  to  the 
conclusion  that  fat  necrosis  may  be  caused  by  an  escape 
of  pancreatic  juice  into  the  abdominal  cavity,  and  al- 
though this  is  no  doubt  the  correct  explanation  in  a  few 
cases  in  which  a  ruptured  duct  is  found  opening  directly 
into  a  peritoneal  cavity,  it  is  probably  not  true  for  the 
majority.  Opie  points  out  that  in  the  experiments  he 
performed  an  escape  of  the  confined  secretion  into  the 
peritoneal  sac  was  not  likely,  for  the  cut  ends  of  the  ducts 
were  found  to  be  surroinided  by  adhesions,  and  the 
condition  of  the  parts  pointed  to  penetration  having 
taken  place  into  the  tissues  about  the  organ,  while  the 
distribution  of  the  lesion,  which  was  most  intense  near 
the  pancreas  and  in  the  structures  anatomically  contin- 
uous with  it,  was  against  its  having  arisen  from  a  flow 
of  pancreatic  juice  over  the  surface  of  the  peritoneum. 
In  order  to  test  the  ability  of  the  pancreatic  secretion 
to  produce  fat  necrosis,  when  directly  injected  into  fat 
tissue,  Opie  arranged  an  experiment  in  which  the  cut 
ends  of  the  pancreatic  ducts  were  made  to  lie  in  the  sub- 
cutaneous tissue  of  the  abdominal  wall.  In  an  animal 
which  survived  the  operation  twenty-seven  days,  he 
found  that  areas  of  fat  necrosis  were  present  in  the  sub- 


200       The  Pancreas:  Its  Surgery  and  Pathology 

cutaneous  tissue  of  the  abdomen  and  thorax,  extending 
in  places  almost  as  far  as  the  vertebral  column,  but  were 
most  abundant  in  the  neighbourhood  where  the  cut  ends 
of  the  ducts  terminated.  Small  areas  were  also  found 
in  the  omentum,  between  the  pancreas  and  the  spleen, 
and  in  the  subperitoneal  tissue  around  the  operation 
wound,  but  none  could  be  found  in  the  duodenal  mesen- 
tery, and  mesentery  of  the  large  intestine,  where  previous 
experiments  had  shown  fat  necrosis  from  simple  ligature 
of  the  ducts  to  be  most  abundant. 

In  a  total  of  twenty-five  cases  of  acute  necrosis  of  the 
pancreas  in  dogs,  produced  by  various  methods,  Gulcke 
found  fat  necrosis  in  all  but  one.  This  animal  died 
within  eight  hours,  possibly  before  there  was  time  for 
fat  necrosis  to  occur.  .  In  most  instances  the  lesion  was 
widely  spread  through  the  abdominal  cavity,  and  in  two 
animals  was  also  found  in  the  mediastinum  and  pericar- 
dium, where  it  followed  the  course  of  the  lymph-vessels. 
In  six  dogs  the  pancreas  was  walled  off  by  tampons  from 
the  remainder  of  the  peritoneal  cavity,  either  at  the  time 
of  the  operation  or  a  few  hours  later.  In  none  of  these 
was  there  any  fat  necrosis  of  the  general  cavity,  although 
it  occurred  along  the  drainage  tract  and  in  the  superficial 
fat.  Gulcke  is  of  opinion  that  these  experiments  prove 
that  fat  necrosis  is  produced  secondarily  as  the  result  of 
a  primary  necrosis  of  the  pancreas  with  direct  diffusion, 
or  absorption,  or  transportation  of  the  pancreatic  secre- 
tion through  the  lymph- vessels. 

Hildebrand  has  suggested  that  obstruction  to  the 
venous  circulation,  by  preventing  the  absorption  of  the 
pancreatic  secretion  by  the  blood,  might  favour  fat  necro- 
sis, but  Opie  maintains  that  in  his  experiments  no  distur- 
bance of  the  circulation  took  place,  and  it  can  therefore 
play  but  a  small  part  in  the  process.  The  absence  of 
hcemorrhagic  infiltration  and  local  ischasmia  in  his  ex- 
periments shows,  Opie  thinks,  that  they  are  not  essential 


Fat  Necrosis  201 

for  the  production  of  fat  necrosis,  in  spite  of  the  views  of 
Katz  and  Winkler  to  the  contrary. 

It  has  already  been  pointed  out  in  a  previous  section 
that  ligature  of  the  pancreatic  ducts  in  animals  gives  rise 
to  chronic  interstitial  inflammation,  and  it  might  there- 
fore be  inferred  that  the  fat  necrosis  produced  by  prevent- 
ing the  flow  of  secretion  in  this  way  is  connected  with  the 
change  of  structure.  Opie  maintains,  however,  that  it  is 
not  an  essential  factor,  for  the  lesion  was  found  in  an 
animal  that  survived  the  operation  but  twenty-four 
hours,  and  was  also  widely  disseminated  in  another  which 
lived  only  four  days  after  ligature  of  the  ducts  and  the 
subsequent  injection  of  pilocarpin. 

When  speaking  of  the  pathology  of  acute  pancreatitis 
we  mentioned  that  not  infrequently  fat  necrosis  was 
found  to  accompany  the  pancreatic  lesion  produced  by 
injecting  various  irritating  and  toxic  substances  into  the 
parenchyma  and  ducts  of  the  gland.  The  experiments 
of  Hlava,  Oser,  and  Flexner  are  particularly  noteworthy 
in  this  connection,  for  they  found  that  injections  of  dilute 
acid,  dilute  alkalies,  artificial  gastric  juice,  turpentine, 
or  suspensions  of  bacteria,  while  causing  more  or  less 
serious  injury  to  the  parenchyma,  are  liable  to  be  accom- 
panied by  necrotic  changes  in  the  pancreatic  and  abdom- 
inal fat. 

Langerhans,  Dettmer,  Hildebrand,  Katz,  and  Winkler 
inferred,  from  their  observations  and  experiments,  that 
the  constituent  of  the  pancreatic  secretion  to  which  fat 
necrosis  was  due  was  the  fat-splitting  ferment,  but  the 
demonstration  of  its  presence  in  the  necrotic  foci  was 
first  made  by  Flexner.  He  showed  that  when  pieces  of 
the  altered  tissue  from  human  and  experimental  cases 
were  allowed  to  act  upon  neutral  butter-fat,  fatty  acids, 
which  could  be  recognized  by  their  reaction  and  odour, 
were  set  free.  Opie  has  since  repeated  the  experiment 
with  portions  of  necrotic  fat  from  the  omentum,  mesen- 


202       The  Pancreas:  Its  Surgery  and  Pathology 

tery,  subcutaneous  tissue,  and  pericardium  in  two  animals 
in  which  fat  necrosis  had  been  produced  by  ligature  of 
the  ducts,  and  obtained  a  well-marked  reaction  in  each 
instance. 

Clinically  disseminated  fat  necrosis  has  been  found  to 
be  associated,  as  a  rule,  with  some  well-marked  lesion  of 
the  pancreas.  In  most  cases  there  has  been  a  haemor- 
rhagic  infiltration  of  the  gland,  accompanied  by  more  or 
less  degeneration  and  necrosis  of  the  parenchyma.  Gan- 
grenous pancreatitis  is  found  somewhat  less  frequently, 
but  sequestration  of  the  gland  may  arise,  as  Langerhans 
suggests,  from  extensive  necrosis  of  the  surrounding  fat. 
Suppurative  inflammation  is  occasionally  accompanied 
by  fat  necrosis,  and  chronic  interstitial  inflammation, 
whether  due  to  blocking  of  the  ducts  or  some  other  cause, 
is  at  times  found  in  association  with  necrotic  changes  in 
the  interstitial  and  surrounding  fat  tissue  of  the  organ. 
Carcinoma  of  the  head  of  the  pancreas  has  been  found 
with  focal  fat  necrosis  in  some  cases. 

It  has  been  usually  said  that  the  presence  of  extensive 
fat  necrosis  is  a  fatal  sign,  but  that  it  is  not  always  so, 
is  shown  by  the  complete  recovery  of  a  case  of  acute  pan- 
creatitis with  well-marked  disseminated  necrosis  that  was 
operated  on  by  one  of  us.  Korte  has  also  met  with  the 
condition  during  life  and  found  that  after  a  time  it  had 
disappeared,  but  in  his  cases  there  had  been  no  evident 
disease  of  the  gland.  Slight  changes  are  not  infrequently 
seen  in  the  pancreas  and  neighbouring  peritoneal  fat 
post-mortem  without  any  marked  alteration  in  the 
structure  of  the  organ,  and  without  there  having  been 
any  symptoms  during  life.  In  these  cases  the  diffusion 
of  pancreatic  juice  is  probably  either  agonal  or  post- 
mortem. Cases  have  been  reported  by  Fraenkel  and 
Flexner,  however,  in  which  there  was  disseminated  fat 
necrosis,  but  no  demonstrable  lesion  of  the  pancreas,  and 
to  which  this  explanation  would  not  apply.     A  case  of 


Fat  Necrosis 


203 


Fig.  94. — Fat  necrosis  of  the  omentum  in  a  case  of  chronic  interstitial 
pancreatitis  (Santos). 


,^Xi-:^J^--^ 


Fig.  95. — Microphotograph  of  an  area  of  fat  necrosis  in  the  same  case 
of  chronic  pancreatitis  (Santos). 


204       The  Pancreas:  Its  Surgery  and  Pathology 

acute  peritonitis  with  fat  necrosis,  unaccompanied  by 
any  discoverable  disease  of  the  pancreas,  has  been  recently 
reported  by  Fawcett  to  the  Clinical  Society  of  London, 
and  Sawyer  has  published  details  of  eight  cases  of  fat 
necrosis,  in  two  of  which  there  was  no  obvious  pancreatic 
lesion.  In  the  first  of  Sawyer's  cases,  death  followed 
hydrochloric  acid  poisoning,  and  post-mortem  there  were 
large  areas  of  fat  necrosis  on  the  surface  of  the  pancreas 
and  in  its  substance.  There  was  no  necrosis,  however, 
beyond  the  region  of  the  pancreas.  The  gland  itself 
' '  seemed  to  be  normal  in  size  and  showed  the  usual  lobu- 
lation." Microscopically  too  it  "appeared  normal."  The 
pancreatic  duct  was,  however,  obstructed  by  inflammatory 
changes,  and  the  duodenum,  and  the  first  twelve  inches  of 
the  jejunum,  were  acutely  inflamed.  Sawyer  attributes 
the  fat  necrosis  in  this  case  to  damage  or  injury  of  the  pan- 
creas by  the  corrosive  poison,  but,  in  the  light  of  Opie's 
experiments,  it  appears  not  improbable  that  stimulation 
of  the  pancreas  by  secretin,  set  free  from  the  intestinal 
mucous  membrane  through  the  action  of  the  hydrochloric 
acid,  may  have  contributed,  or  even  brought  about,  the 
result,  especially  as  there  was  some  obstruction  of  the 
duct.  In  the  second  case  the  condition  was  found  in 
association  with  mitral  stenosis,  with  infarcts  of  the 
kidneys  and  spleen,  many  of  which  were  recent.  The 
fat  necrosis  chiefly  affected  the  surface  and  substance  of 
the  pancreas,  but  a  few  points  were  also  found  in  the  root 
of  the  mesentery.  Microscopically  a  few  small  areas  of 
necrosis  of  the  gland  tissue  were  found  which  Sawyer 
thinks  may  have  arisen  from  multiple  emboli,  although 
no  thrombosis  of  the  vessels  could  be  demonstrated. 
To  the  setting  free  of  the  fat-splitting  ferment  from  these 
areas  he  attributes  the  fat  necrosis,  but  it  is  also  noted 
that  the  patient  was  slightly  jaundiced,  suggesting  that 
there  may  have  been  some  catarrhal  pancreatitis. 


Fat  Necrosis  20= 


Literature 

Balser:    Arch.  f.  path.  Anat.,  1882,  xc,  520.     Verhandl.  d.  XI  Cong.  f. 

innere  Med.,  1892,  S.  450. 
Blume:    Beitrage  zum  Wissenschaft.  Med.,  Festschrift  zum  Naturfor- 

scheinersanimlung  in  Braunschweig,   1897,  S.   139. 
Chiari:    Prager  med.  Wochenschr.,  1883,  xxx,  255. 
Dettmar:    Inaug.   Dissert.,   Gottingen,    1895. 
Dieckoff:    "Beitrage  zur  path.  Anat.  des  Pankreas, "  1896. 
Fawcett:    Lancet,  Dec.  i,  1906,  p.  151 2. 
Fitz:  New  York  Med.  Record,  1889,  Nos.  8-10.     Boston  Med.  and  Surg. 

Journ.,  1892. 
Flexner:    Journ.  Exper.  Med.,  1897,  ^^'  493-      Proc.  Path.  Soc.  Phila., 

1899,  New  Series,  iii,  25. 
Fraenkel:    Muncher  med.  Wochenschr.,  1896,  xHii,  813. 
Gulcke:   Archiv.  f.  kUn.  Chir.,  Ixxxvii,  Heft  4. 
Hansemann:    Berl.  med.  Gesellsch.,   1889.     JBerl.  khn.  Wochenschr., 

1889. 
Heidenhain  and  Gottlieb:   Arch.  f.  exper.  Path.  u.  Pharmakol.,  1894, 

xxxiii,  261. 
Heller:  Schmidt's  Jahrb.,  i860,  cv,  306. 
Hildebrand:   Centralbl.  f.  Chir.,  1895,  ^^'  297- 
Hlava:   Arch,  bohem.,  1890,  iv,  139. 
Jung:    Inaug.  Dissert.,  Gottingen,  1895. 

Katz  and  Winkler:    "Die  multiple  Fettgewebsnecrose, "  Berlin,  1899. 
Korte:    XXIII  Surgical  Congress,  1894.      Berl.  Klinik,  1896,  cii,  i. 
Langerhans:     Berliner  klin.    Wochenschr.,     1889,    S.    1114.     Arch.   f. 

path.  Anat.,  1890,  cxxii,  252.     Festschr.  Rudolf  Virchow,  1891. 
Milisch:    Inaug.  Dissert.,  Berlin,  1897. 
Olt:   Deutsche  Thieratztl.  Wochenschr.,  189S,  vi,  117. 
Opie:   Johns  Hopkins  Hosp.  Rep.,  ix,  859. 
Oser:    "Diseases  of  the  Pancreas,"  Nothnagel's  "Encvclop.  of  Pract. 

Med."  (Eng.  tr.). 
Ponfick:  Verhandl  d.  Congr.  f.  innere  Med.,  1892,  S.  549.      Berliner  klin. 

Wochenschr.,  1896,  xvii. 
Sawyer:    Lancet,  Jan.  19,   1907,  p.   158. 
Seitz:    Zeitschr.  f.  klin.  Med.,  1892,  S.  i. 
Steven,  Lindsay:    Lancet,  1894,  i,  963. 
Williams:    Boston  Med.  and  Surg.  Journ.,  1897,  cxxxvi,  345. 


CHAPTER  X 
CHEMICAL  PATHOLOGY 

The  chemical  changes  induced  in  the  body  by  diseases 
of  the  pancreas  may  be  considered  under  two  headings: 
first,  those  which  are  connected  with  the  processes  of 
digestion;  and,  secondly,  those  which  result  from  dis- 
turbances of  internal  metabolism  and  are  shown  by  altera- 
tions in  the  blood,  urine,  etc.  No  hard  and  fast  line  can 
be  drawn,  however,  between  the  two,  and,  as  we  shall  see 
later,  disturbances  of  digestion  are  liable  to  affect  the 
internal  economy  of  the  body,  not  only  through  the  direct 
effects  they  exert  upon  nutrition,  but  also  by  the  forma- 
tion of  various  toxic  substances,  which,  being  absorbed 
from  the  intestine,  give  rise  to  alterations  in  the  blood 
and  other  tissues,  and  also  produce  changes  in  the  urine. 

The  most  important  digestive  disturbances,  due  to 
disease  of  the  pancreas,  arise  from  absence  or  diminution 
of  its  secretion.  Obstruction  of  the  pancreatic  duct, 
from  the  pressure  of  tumours,  or  from  calctdi  in  the  com- 
mon bile-duct,  or  in  the  pancreatic  ducts  themselves,  is 
the  commonest  condition  to  give  rise  to  more  or  less 
complete  absence  of  the  secretion  from  the  intestine, 
but  atrophy,  fatty  degeneration,  or  sclerosis  of  the  gland 
may  occasionally  advance  so  far  as  to  destroy  practically 
the  whole  of  the  secreting  parenchyma. 

In  less  advanced  cases  the  secretion  may  be  impaired, 
and  in  these,  and  in  inflammatory  lesions  arising  from 
whatever  cause,  the  secretory  activity  is  diminished,  to 
a  degree  corresponding  to  the  extent  and  intensity  of  the 
lesion.     Among  the  commonest  causes  of  impaired  secre- 

206 


Chemical  Pathology  207 

tion  are  acute  and  chronic  catarrhs  of  the  duodenum, 
often  combined  with  gastritis,  general  enteritis,  and  coli- 
tis. These  may  directly  affect  the  secretion  by  giving 
rise  to  a  catarrhal  pancreatitis,  but  may  also  indirectly 
exert  an  action  on  the  digestive  processes  by  interfering 
with  the  supply  of  enterokinase  by  which  the  proteolytic 
ferment  of  the  pancreas  is  activated  under  normal  condi- 
tions. Temporary  checking  of  the  secretion,  or  a  chronic 
diminution  in  the  amount,  is  said  by  Herter  to  occur  in 
prostrating  illnesses  and  from  fever,  anaemia,  extreme 
nervous  exhaustion,  fright,  grief,  mental  overwork, 
worry,  and  excessive  muscular  or  sexual  fatigue.  Stol- 
nikow,  investigating  the  condition  of  the  secretion  in 
fever,  found  that  it  was  diminished,  and  finally  ceased, 
although  the  gland  itself  was  never  quite  free  from  fer- 
ment. 

Little  is  known  concerning  excessive  pancreatic  secretion. 
The  flow  of  pancreatic  juice  and  that  of  saliva  are  known 
to  be  both  stimulated  by  the  administration  of  pilocarpin. 
Fats  also  favour  the  formation  and  secretion  of  pancreatic 
juice,  and,  as  we  have  seen,  the  gland  is  powerfully  stimu- 
lated by  the  presence  of  hydrochloric  acid  in  the  upper 
part  of  the  small  intestine,  so  that  in  hyperchlorhydria 
it  is  possible  that  a  quantity  in  excess  of  the  requirements 
of  the  food  may  be  secreted.  It  is  also  possible  that  in 
the  early  stages  of  the  inflammatory  lesions  of  the  gland 
there  may  be  an  increased  flow  of  secretion,  corresponding 
to  the  salivation  that  occurs  in  inflammatory  affections 
of  the  salivary  glands. 

Starling  has  proved  that  a  mixture  of  pancreatic  juice 
and  intestinal  secretion  has  an  extraordinarily  powerful 
action  on  the  walls  of  the  bowel,  producing  inflammation 
and  erosions,  so  that  it  is  not  unlikely  that  an  excessive 
secretion  may  give  rise  to  a  more  or  less  marked  enteritis, 
with  consequent  diarrhoea.  Senn  has  suggested  that 
there  is  a  causal  relationship  between  the  profuse  diar- 


2o8       The  Pancreas:  Its  Surgery  and  Pathology 

rhoea,  seen  at  times  with  cysts  and  degenerations  of  the 
pancreas,  and  the  glandular  changes. 

The  digestive  disturbances  likely  to  result  from  absence 
or  a  diminution  of  the  secretion  may  be  inferred  from  a 
knowledge  of  its  physiological  functions.  Since  it  is  the 
most  important  of  all  the  digestive  fluids,  and  exerts  an 
action  upon  each  of  the  three  principal  classes  of  food 
material,  any  interference  with  its  activities  may  be 
expected  to  lead  to  defective  assimilation  of  fats,  proteids, 
and  carbohydrates,  and  an  examination  of  the  faeces 
should  show  that  an  abnormally  high  proportion  of  the 
food  is  passed  in  an  undigested  state. 

The  preparation  of  fats  for  absorption  by  the  intestine 
is  peculiarly  a  function  of  the  pancreatic  juice,  and  it  is 
to  the  investigation  of  undigested  fat  in  the  stools  in 
lesions  of  the  pancreas  that  the  attention  of  experimen- 
talists and  clinicians  has  therefore  been  chiefly  devoted. 
Claude  Bernard  pointed  out  that,  when  the  pancreas  was 
destroyed  by  injecting  oil  into  the  main  duct,  an  abnormal 
amount  of  fat  was  present  in  the  fceces,  often  in  such 
quantities  as  to  coat  them  with  an  oily  covering,  and  while 
his  results  were  confirmed  by  some  observers,  they  were 
contradicted  by  others,  who  subsequently  carried  out 
similar  investigations. 

A  series  of  careful  experiments  upon  dogs  carried  out 
by  Abelmann,  under  the  direction  of  Minkowski,  were  the 
first  to  really  place  the  matter  on  a  sure  footing,  and  to 
clearly  demonstrate  that  when  the  pancreatic  secretion  is 
prevented  from  entering  the  intestine,  or  is  diminished  in 
amount,  by  complete  or  partial  extirpation  of  the  gland, 
the  digestion  and  absorption  of  fat  contained  in  the  food 
are  more  or  less  seriously  interfered  with.  He  found 
that  when  the  pancreas  was  entirely  removed,  non-emul- 
sified fat  was  not  absorbed  at  all,  and  emulsified  fat  only  to 
a  slight  extent  (18.5  per  cent.).  Animals  from  which 
the  pancreas  had  been  partly  removed  showed  better 


Chemical  Pathology  209 

absorptive  powers,  but  their  capacity  in  this  direction 
was  limited,  for  whereas  small  amounts  of  emulsified  fats 
were  about  half  absorbed,  larger  amounts,  70  to  150 
grams,  were  less  efficiently  dealt  with.  A  natural  emul- 
sion of  fat  in  the  form  of  milk  was  much  more  completely 
utilised  in  both  instances,  30  jjer  cent,  of  large  amounts 
and  53  per  cent,  of  smaller  quantities  being  absorbed 
when  the  pancreas  had  been  completely  extirpated,  and 
up  to  80  per  cent,  when  portions  of  the  gland  had  been 
left  behind.  The  administration  of  pig's  pancreas  with 
the  food  was  found  to  facilitate  the  absorption  of  fats, 
and  pointed  to  the  absence  of  the  pancreatic  secretion 
being  the  main  cause  of  their  defective  assimilation. 
Abelmann  consequently  concluded  that  all  fats,  with  the 
exception  of  milk,  unquestionably  need  the  influence  of 
the  pancreas  for  their  utilization.  Sandmeyer  in  his 
experiments  obtained  similar  but  less  consistent  results. 
He  also  found  that  the  absorption  of  fat  was  increased  by 
the  addition  of  fresh  pancreas  to  the  food.  After  ex- 
tirpating the  pancreas  in  a  dog  Cavazzani  found  that 
unused  fat  was  present  in  the  faeces,  and  that,  while  the 
animal  ate  soap  with  great  eagerness,  it  rejected  fat. 
Baldi  observed  a  large  amount  of  oily  fat,  which  did  not 
solidify  at  the  temperature  of  the  room,  in  the  fseces  of 
depancreatised  dogs  fed  on  meat  from  which  the  fat  had 
been  removed,  but  was  unable  to  produce  so  high  a  de- 
gree of  steatorrhoea  by  tying  the  bile-duct.  Rosenberg 
produced  atrophy  of  the  pancreas  by  tying  the  vessels 
and  cutting  the  duct ;  he  then  found  that  the  f^ces  were 
bulky,  clay-coloured,  and  contained  a  large  amount  of 
fat. 

These  experiments  show  that  in  animals  extirpation, 
or  destruction  of  the  pancreas  is  attended  by  a  defective 
absorption  of  fat,  except  that  of  milk,  and  that  while  simi- 
lar but  less  marked  effects  can  be  produced  by  exclud- 
ing bile  from  the  intestine,  the  increased  proportion  of  fat 
14 


2IO       The  Pancreas:  Its  Surgery  and  Pathology 

in  the  stools  is  to  be  mainly  attributed  to  absence  of  the 
pancreatic  secretion. 

Analysis  of  the  faeces  in  Abelinann's  experiments 
showed  that  from  30  to  85  per  cent,  of  the  non-emulsified 
fat  had  undergone  cleavage  into  fatty  acids  and  soaps. 
He  concluded  therefore  that,  after  total  extirpation,  fat 
cleavage  was  not  disturbed.  Katz,  however,  investigat- 
ing the  condition  of  the  faeces  in  a  dog  operated  on  by 
Oser,  found  that  there  was  "a  surprising  diminution" 
in  the  cleavage  of  fat,  after  partial  extirpation  of  the 
pancreas  and  tying  the  main  excretory  duct,  51.53  per 
cent,  being  neutral  fat,  46.04  per  cent,  fatty  acid,  and 
2.33  per  cent,  soaps. 

Opportunities  of  investigating  the  effects  of  simple 
and  complete  exclusion  of  the  pancreatic  secretion  from 
the  intestine  in  man  are  rare,  for  total  degeneration  of 
the  secreting  parenchyma  is  exceptional,  and  when  the 
duct  of  Wirsung  is  blocked  the  results  of  an  associated 
biliary  obstruction  that  usually  occurs  have  also  to  be 
taken  into  account.  Most  of  the  published  observations 
therefore  relate  to  cases  in  which  the  digestive  functions 
of  the  pancreas  have  been  more  or  less  interfered  with, 
but  yet  not  completely  abolished,  and  in  some  the  results 
have  been  complicated  by  a  simultaneous  interference 
with  the  flow  of  bile  into  the  intestine.  The  majority  of 
authors  have  been  satisfied  with  a  naked-eye  description 
of  the  faeces,  and  although  the  more  striking  variations 
from  the  normal  can  be  recognized  in  this  way,  it  gives 
no  precise  data  on  which  to  base  an  opinion  as  to  fre- 
quency of  an  excess  of  fat  in  the  stools  in  disease  of  the 
pancreas,  and  furnishes  no  criterion  by  which  the  fat 
contents  can  be  compared  in  different  lesions  of  the  gland, 
or  with  that  in  the  dejecta  in  other  disorders.  Ziehl,  in 
1883,  published  an  account  of  a  case  of  carcinoma  of  the 
pancreas,  with  jaundice,  in  which  he  found  that  about 
50  per  cent,  of  the  dried  faeces  consisted  of  fat.     Demme 


Chemical  Pathology  211 

investigated  the  stools  from  a  case  of  congenital  syphilis 
with  jaundice,  gummata  of  the  liver,  and  atrophy  of  the 
pancreas,  and  found  from  64  per  cent,  to  73.3  per  cent, 
of  fat.  Weintraud's  patient  lost  in  the  faeces  from  22  to 
25  per  cent,  of  the  fat  taken  as  food,  a  considerable  excess 
over  the  7  to  11  per  cent,  normally  undigested,  and  in 
Deucher's  two  patients  the  loss  was  still  more  marked, 
being  52.8  per  cent,  and  83  per  cent,  respectively.  In  a 
case  of  cancer  of  the  pancreas  in  which  the  faeces  were 
examined  over  a  month  before  the  onset  of  jaundice, 
Oser  found  that  45.9  per  cent,  of  the  dry  weight  consisted 
of  fat,  and  that  this  was  almost  entirely  neutral  fat. 
Numerous  fat-needles  and  fat-drops  were  seen  micro- 
scopically. On  the  other  hand,  Miiller  was  not  able  to 
detect  any  increase  of  fat,  either  macroscopically,  micro- 
scopically, or  chemically,  in  the  cases  of  obliteration  and 
cystic  degeneration  of  the  pancreas  that  he  investigated. 
He  attributed  the  steatorrhoea  in  such  cases  entirely  to 
the  absence  of  bile,  and  stated  that  when  bile  was  excluded 
from  the  intestine  from  55.2  to  75.5  per  cent,  of  the  fat 
contained  in  food  was  passed  unabsorbed,  as  against  the 
normal  7  to  11  per  cent.  The  same  observer,  investigat- 
ing three  cases  of  obstruction  of  the  duct  of  Wirsung, 
with  degeneration  of  the  gland,  found  that,  although  the 
total  quantity  of  fat  absorbed  was  not  far  from  the  normal, 
the  cleavage  of  fats  in  the  intestine  was  very  considerably 
diminished,  for  only  39.8  per  cent,  of  the  fat  in  the  faeces 
was  found  to  be  split  into  fatty  acids  and  soaps,  instead 
of  the  normal  of  about  84  per  cent. 

Our  own  observations  on  the  fat  contents  of  the  fcFces 
m  diseases  of  the  pancreas  have  been  mainly  carried  out 
by  a  special  method,  described  by  one  of  us  at  the  Leices- 
ter meeting  of  the  British  Medical  Association  in  1905. 
This,  while  much  more  rapid  than  the  Soxhlet  process, 
gives  results  that  are  satisfactory  for  clinical  work  and 
for  purposes  of  comparison.     It  is  carried  out  as  follows : 


212       The  Pancreas:  Its  Surgery  and  Pathology 

Two  clean,  dry,  Schmidt-Stokes  milk-tubes,  labelled 
A  and  B,  and  provided  with  a  lo  c.c.-mark,  are  taken, 
and  into  the  lower  bulb  of  each  is  introduced  an  accu- 
rately weighed  quantity  (about  half  a  gram)  of  the  finely 
powdered  faeces,  that  have  been  dried  to  a  constant 
weight  on  a  water-bath.  The  residue  on  the  watch-glass 
used  for  weighing,  and  on  the  sides  of  the  short-necked 
funnel  with  which  the  powder  is  introduced  into  the 
tube,  is  washed  down  with  a  fine  jet  from  a  wash-bottle, 
which  for  the  A-tube  contains  hydrochloric  acid  (1:3), 
and  for  the  B-tube  plain  water.  The  sides  of  the  tube 
are  also  washed  until  the  whole  of  the  sample  is  collected 
in  the  lower  bulb,  and  the  10  c.c-mark  is  reached.  The 
A-tube  is  then  heated  in  boiling  water  for  twenty  minutes, 
occasionally  rotating  it  so  as  to  well  mix  the  contents. 
After  cooling,  both  tubes  are  filled  to  the  50  c.c.-mark 

with  ether,  securely 
4      (      >..|....|....|..'..|.v.|....|....[....|....|^  I  ^     corked,  and  inverted 

Fig.  96.— Schmidt-Stokes  milk-tube.         forty  times,  taking 

care  that  the  whole 
of  the  solid  material  runs  through  at  each  turn.  Each  tube 
is  then  rotated  between  the  hands,  and  allowed  to  stand  for 
half  an  hour  or  more,  in  order  that  the  solid  residue  may  be 
collected  into  the  lower  bulb.  Considerable  care  is  neces- 
sary in  carrying  out  this  part  of  the  process  in  some  in- 
stances, or  a  perfectly  clear  supernatant  layer  of  ether,  free 
from  solid  particles,  is  not  secured.  With  a  pipette,  exactly 
20  c.c  of  the  clear  ethereal  extract  are  drawn  off  from  each 
tube  and  delivered  into  two  C02-fiasks  of  known  weight, 
the  amount  of  ether  left  in  the  tubes  being  noted.  The 
ether  in  the  flasks  is  then  evaporated,  the  residue  dried 
on  the -water-bath,  and  the  flasks  again  weighed.  From 
the  amount  of  extract  yielded  by  20  c.c.  of  ether,  and 
the  quantity  of  ether  left  in  the  tubes,  the  total  amount 
yielded  by  the  weight  of  dried  f^ces  used  may  be  calcu- 
lated, and  from  this  the  percentage  in  the  stool  determined. 


Chemical  Pathology  213 

The  result  from  the  A-tube  gives  the  total  fat  in  the  faeces, 
including  the  neutral  fats,  free  fatty  acids,  and  combined 
fatty  acids,  or  soaps,  since  the  latter  will  have  been 
decomposed  by  being  boiled  with  the  hydrochloric  acid  and 
thuc  rendered  soluble;  that  from  the  B-tube  represents 
the  neutral  fats  and  fatty  acids  only,  as  the  soaps  will 
remain  undissolved  by  the  ether:  the  difference  between 
the  two  will  therefore  give  the  proportion  of  saponified 
fat  present.  Other  substances  in  the  faeces  soluble  in 
ether,  such  as  cholesterin,  lecithin,  cholic  acid,  and  pig- 
ments, are  included  in  the  estimates,  but  as  the  quantity 
is  small  it  does  not  appreciably  affect  the  results.  For 
convenience  of  reference  we  shall  speak  of  the  yield  from 
the  A-tube  as  "total  fat,"  that  from  the  B-tube  as  "neu- 
tral fat,"  and  the  difference  between  the  two  as  "fatty 
acid." 

The  solid  residue  from  the  B-tube  can  be  used  for  the 
detection  of  stercobilin.  For  this  purpose  it  is  filtered 
off,  extracted  with  acid  alcohol,  the  extract  neutralised 
with  ammonia,  and  mixed  with  an  equal  quantity  of  10 
per  cent,  zinc  acetate  in  alcohol.  The  precipitate  that 
forms  is  removed  by  filtration,  and  the  clear  filtrate  ex- 
amined with  a  lens,  against  a  black  background,  for  the 
green  fluorescence  that  indicates  the  presence  of  sterco- 
bilin. The  intensity  of  the  colour  varies  with  the  amount 
of  pigment,  so  that  by  always  using  approximately  the 
same  proportion  of  faeces  and  of  the  reagents  any  marked 
variation  from  the  normal  can  be  detected. 

We  have  examined  over  three  hundred  specimens  of 
faeces  by  these  methods,  but  taking  a  consecutive  series  of 
one  hundred  recent  cases,  in  which  it  has  been  possible 
to  determine  the  condition  of  the  pancreas  and  biliary 
passages  at  operation  or  post-mortem,  and  comparing 
the  results  with  those  obtained  in  sixteen  normal  speci- 
mens, they  may  be  classified  as  follows: 


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214 


Chemical  Pathology  215 

It  will  be  seen  that  the  percentage  of  "total  fat"  in 
the  fcEces  has,  as  a  rule,  been  in  excess  of  the  normal  in 
those  cases  in  which  there  was  reason  to  believe  that  there 
was  a  lesion  of  the  pancreas.  In  one  case  of  malignant 
disease  of  the  head  of  the  gland  as  much  as  93  per  cent, 
was  found  to  be  present,  and  in  no  instance  has  it  fallen 
below  40  per  cent.,  the  average  amount  being  77  per  cent. 
Chronic  pancreatitis,  associated  with  obstruction  of  the 
common  bile-duct,  appears  in  severe  cases  to  interfere 
almost  as  much  with  the  fat  digestion  as  malignant  disease, 
for  82  per  cent,  was  found  in  one  instance,  where  there 
was  jaundice,  and  76  per  cent,  in  another,  where  there 
was  no  discolouration  of  the  skin  and  bile -pigment  was 
absent  from  the  urine.  That  the  high  proportion  of  fat 
met  with  in  some  of  these  cases  is  not  entirely  due  to  the 
biliary  obstruction  is  shown  by  the  fact  that  as  great  an 
excess  has  been  met  with  in  others  in  which  no  obstruc- 
tion to  the  free  flow  of  bile  into  the  intestine  was  present. 
Simple  biliary  obstruction,  not  associated  with  pancreatic 
disease,  may,  however,  cause  a  very  considerable  increase 
of  fat  in  the  stools,  so  that  in  those  cases  where  there  is 
both  obstruction  of  the  common  bile-duct  and  disease 
of  the  pancreas  both  probably  influence  the  result.  Al- 
though severe  or  wide-spread  inflammation  of  the  pan- 
creas would  appear  to  always  give  rise  to  a  certain  amount 
of  steatorrhoea,  we  have  repeatedly  met  with  cases  of 
pancreatitis  in  which  the  proportion  of  fat  in  the  fseces 
was  normal,  or  even  subnormal,  but  these  have  been  of  a 
mild  type  and  generally  in  an  eaHy  stage  where  the  head 
of  the  gland  only  was  involved. 

On  comparing  the  proportions  of  "neutral  fat"  and 
"fatty  acid,"  as  indicating  the  degree  to  which  the  proc- 
ess of  saponification  has  been  carried  in  the  intestine, 
we  see  that  in  simple  pancreatitis,  not  associated  with 
jaundice,  the  former  was  usually  much  in  excess  of  the 
latter,  whereas  in  cases  of  biliary  obstruction,  not  accom- 


2i6       The  Pancreas:  Its  Surgery  and  Pathology 

panied  by  pancreatic  changes,  the  reverse  was  generally 
found.  The  effect  produced  by  the  coexistence  of  pan- 
creatic disease  and  biliary  obstruction  would  appear  to 
depend  upon  the  relative  extent  and  standing  of  the  two 
conditions,  for  whereas  in  malignant  disease  of  the  head 
of  the  pancreas  the  "neutral  fat"  has  always  been  in 
excess  of  the  "fatty  acid,"  the  latter  in  some  cases  of 
recent  pancreatitis  with  gall-stone  obstruction  has  been 
found  to  preponderate.  It  must  be  remembered,  how- 
ever, that  even  the  total  absence  of  pancreatic  juice  and 
bile  does  not  necessarily  put  an  end  to  the  fat-splitting 
process  in  the  intestine,  for,  under  the  influence  of  organ- 
isms of  the  colon  group,  the  conversion  of  fats  into  gly- 
cerine and  fatty  acids  may  go  on  energetically  in  the  lower 
part  of  the  small  intestine,  but  since  the  absorption  of  these 
products  will  be  interfered  with  by  the  absence  of  bile 
and  the  situation  in  which  the  process  takes  place,  they 
will  be  excreted  to  a  large  extent  in  the  faeces.  The  pres- 
ence of  a  higher  proportion  of  saponified  fat  in  the  stools 
in  some  cases  of  malignant  disease  and  serious  pancrea- 
titis than  might  at  first  sight  be  expected  is  probably  to 
be  explained,  at  least  in  part,  in  this  way. 

The  different  results  obtained  on  examining  the  faeces 
in  apparently  similar  cases  is  shown  by  a  series  of  analy- 
ses we  have  recently  had  the  opportunity  of  making  in 
two  instances  of  pancreatic  disease  associated  with  biliary 
fistulas.  The  second  also  illustrates  the  beneficial  effects 
that  may  be  produced  by  suitable  treatment  even  in 
advanced  and  serious  cases  of  pancreatitis.  In  the  first 
case  the  biliary  fistula  formed  after  an  operation  for 
gall-stones  undertaken  by  another  surgeon,  for  whom  an 
examination  of  the  urine  and  faeces  had  been  made  for 
diagnostic  purposes  by  one  of  us.  The  fasces  were  then 
found  to  be  neutral  in  reaction,  of  a  light  brown  colour, 
and  to  contain  a  fair  amount  of  stercobilin.  Chemical 
examination  showed: 


Chemical  Pathology  217 

Organic  matter 84.7% 

Total  fat 4 1.9% 

f  Neutral  fat 26.4% 

\  Fatty  acid i5-5% 

Organic  matter  not  fat 42.8% 

Inorganic  ash iS-3% 

On  a  second  examination  being  made  six  months  later, 
no  stercobilin  could  be  found  in  the  fasces,  they  were 
alkaline  in  reaction,  and  of  a  greasy  white  appearance. 
Chemical  analysis  showed : 

Organic  matter 85.8% 

Total  fat 85.5% 

/  Neutral  fat 35-6% 

\  Fatty  acid 49-9% 

Organic  matter  not  fat o-3% 

Inorganic  ash 14.2% 

An  increase  of  34.4  per  cent,  in  the  "fatty  acid"  as  com- 
pared with  9.2  per  cent,  in  the  "neutral"  fat. 

In  the  second  case  the  patient  had  a  biliary  fistula 
when  he  came  under  our  observation.  The  faeces  were 
white  and  shining,  acid  in  reaction,  and  contained  only  a 
faint  trace  of  stercobilin.  Microscopically  crowds  of  fat 
globules,  fat  crystals,  and  undigested  muscle  fibres  were 
found.  Chemical  examination  gave  the  following  re- 
sults : 

Organic  matter 93-o% 

Total  fat 72.6% 

/  Neutral  fat 69.7% 

\  Fatty  acid 2.9% 

Organic  matter  not  fat 20.4% 

Inorganic  ash 7-o% 

A  fortnight  after  this  examination  had  been  made  he 
was  operated  on  by  one  of  us  and  a  cholecytenterostomy 
performed.  No  gall-stones  were  found  at  the  time  of 
operation,  but  the  pancreas  was  dense,  hard,  and  rugged, 
and  closely  gripped  the  common  bile-duct,  which  passed 
through  it.  Examination  of  the  fasces  a  month  later, 
when  the  patient  had  returned  to  a  normal  mixed  diet, 
showed  that  they  were  of  a  light  yellow,  almost  white, 
colour,  acid  in  reaction,  and  contained  many  fat  globules, 


2i8       The  Pancreas:  Its  Surgery  and  Pathology 

fat  crystals,  and  some  undigested  muscle  fibre.     Chemi- 
cally the  following  results  were  obtained : 

Organic  matter 93- 1% 

Total  fat 68.2% 

/  Neutral  fat 65.7% 

\  Fatty  acid 2.5   % 

Organic  matter  not  fat 24.9% 

■  Inorganic  ash 6.9% 

The  patient  was  then  placed  upon  "pancreon,"  and  it 
was  found,  when  the  faeces  were  examined  five  months 
subsequently,  that  they  were  still  of  a  light  colour,  al- 
though they  contained  a  normal  amount  of  stercobilin, 
the  reaction  was  acid,  and  microscopically  a  few  fat  glo- 
bules, fat  crystals,  and  some  muscle  fibres  were  present. 
The  chemical  analysis  gave : 

Organic  matter 93.2% 

Total  fat 40.2% 

/Neutral  fat 26.1% 

\  Fatty  acid i4-i% 

Organic  matter  not  fat S3-o% 

Inorganic  ash 6.8% 

Turning  the  bile  into  the  intestine  thus  produced  prac- 
tically no  change  in  the  fat  content  of  the  fseces,  but  when 
the  deficiency  of  pancreatic  juice  was  partly  supplied 
by  the  administration  of  "pancreon"  the  neutral  fat  was 
diminished  over  40  per  cent,  and  the  fatty  acid  increased 
II  per  cent.,  while  the  amount  of  unabsorbed  fat  in  the 
stools  was  also  very  considerably  diminished. 

In  most  of  our  investigations  on  the  fseces  in  pancreatic 
disease  the  patients  have  been  upon  an  ordinary  mixed 
diet,  and,  for  purposes  of  clinical  diagnosis,  we  have  found 
that  this  is  quite  sufficient,  and  that  it  is  not  necessary 
to  delay  the  examination  of  the  stools  until  a  uniform 
fixed  standard  of  diet  has  been  established.  It  is  neces- 
sary, however,  that  the  character  and  amount  of  the 
food  should  be  borne  in  mind  when  the  results  of  the 
chemical  analysis  are  considered,  for  some  fats  are  more ' 
readily  absorbed  than  others,  and  large  quantities  might 


Chemical  Pathology  219 

pass  through  the  intestine  unchanged  even  in  normal 
persons.  We  have  already  mentioned  that  exxjerimental 
investigations  on  depancreatised  animals  have  proved 
that  a  natural  emulsion,  such  as  milk,  is  more  readily 
dealt  with  than  fats  in  the  solid  form,  and  there  is  evidence 
which  shows  that  the  chemical  constitution  of  the  latter 
is  also  not  without  influence  upon  their  susceptibility  to 
digestive  processes.  As  a  general  rule,  it  may  be  stated 
that  the  lower  the  melting-point  of  a  fat  employed  as 
food,  the  more  completely  will  it  be  absorbed;  thus, 
olein  is  more  readily  utilised  by  the  organism  than  pal- 
mitin  or  stearin,  and  food  materials  containing  the  for- 
mer are  not  so  likely  to  appear  unchanged  in  the  faeces 
as  those  containing  the  latter.  In  a  case  of  cancer  of  the 
head  of  the  pancreas,  with  complete  biliary  obstruction, 
we  found  that  when  the  patient  was  upon  a  mixed  diet 
the  dried  fasces  contained  58.7  per  cent,  of  "total  fat," 
41.4  per  cent,  of  "neutral  fat,"  and  17.5  per  cent,  of 
"fatty  acid";  on  a  milk  diet,  however,  the  "total  fat" 
was  reduced  to  26.2  per  cent.,  the  "neutral  fat"  to  25.9 
per  cent.,  and  the  "fatty  acid"  to  0.3  per  cent. 

The  digestibility  of  fat,  in  the  form  of  meat,  is  also 
influenced  to  a  certain  extent  by  the  condition  of  the 
gastric  secretion.  We  mentioned,  when  considering  the 
physiology  of  pancreatic  digestion,  that  collagen  is  not 
acted  upon  by  pancreatic  secretion;  fat,  therefore,  which 
is  enclosed  in  a  mesh  of  connective  tissue  is  liable  to  be 
protected  from  digestion  in  the  intestine  unless  it  has 
been  previously  acted  upon  in  the  stomach,  so  that  defi- 
ciency or  absence  of  hydrochloric  acid  in  the  stomach 
may  lead  to  the  appearance  of  an  abnormal  proportion 
of  fat  in  the  fasces. 

An  excessively  fatty  diet  may  also  increase  the  fat 
content  to  an  unusual  degree,  both  normally  and  in 
cases  of  disease  of  the  pancreas.  In  this  connection  we 
may  mention  that  we  have  found  that  in  some  apparently 


220       The  Pancreas:  Its  Surgery  and  Pathology 

healthy  persons  there  appears  to  be  an  inability  to  digest 
more  than  a  very  limited  amount  of  fat,  and,  as  their 
powers  in  this  direction  can,  at  least  in  some  instances,  be 
improved  by  the  administration  of  preparations  of  pan- 
creas, it  is  possible  that  the  difficulty  is  due  to  a  congenital 
or  acquired  deficiency  of  that  organ. 

In  addition  to  diseases  of  the  pancreas,  biliary  obstruc- 
tion, defective  gastric  digestion,  and  excess  of  fat  in  the 
food,  abnormal  quantities  of  fat  may  be  passed  in  the 
faeces  from  faulty  absorption,  due  either  to  disease  of  the 
intestinal  mucous  membrane  or  to  obstruction  of  the 
lymphatics.  Such  conditions  are,  however,  compara- 
tively rare,  and  are  chiefly  met  with  in  extreme  intestinal 
tuberculosis,  amyloid  disease,  sprue,  etc.  Salomon  states 
that  purely  functional  disturbances  of  fat  digestion  may 
occur,  but  there  is  as  yet  little  to  substantiate  this.  The 
recognition  and  differentiation  of  the  steatorrhoea  met 
with  in  these  conditions  from  that  due  to  pancreatic  disease 
can  only  be  arrived  at  by  attention  to  other  signs,  for  the 
steatorrhoea  itself  presents  no  special  characters  by  which 
it  can  be  recognised.  Thus  in  a  case  of  intestinal  tuber- 
culosis we  found  that  the  "total  fat"  constituted  33.1 
per  cent,  of  the  dry  weight  of  the  faeces,  and  that  21.4 
per  cent,  of  this  was  "neutral  fat"  and  11. 7  per  cent, 
"fatty  acid."  In  another  patient  suffering  from  the 
same  disease  the  faeces  were  found  to  contain  61.3  per 
cent,  of  "total  fat,"  42.5  per  cent,  of  "neutral  fat,"  and 
18.8  per  cent,  of  "fatty  acid"— figures  which  closely 
resemble  those  met  with  in  steatorrhoea  of  pancreatic 
origin.  We  have  also  had  the  opportunity  of  examining 
the  faeces  from  a  considerable  number  of  cases  diagnosed 
as  sprue,  and  in  all  have  found  a  large  excess  of  fat,  which 
consisted  chiefly  of  "neutral  fat."  Although  there  is  no 
doubt  that,  in  this  disease,  the  steatorrhoea  is  in  part  due 
to  defective  absorption,  from  atrophy  of  the  mucous 
membrane  of  the  intestine,  we  have  come  to  the  conclu- 


Chemical  Pathology  221 

sion  that,  in  some  instances  at  least,  the  condition  is 
contributed  to  by  concurrent:  disease  of  the  pancreas. 
In  one  case  of  this  description,  in  which  we  had  reason 
to  believe,  from  an  examination  of  the  urine  and  faeces, 
that  the  pancreas  was  diseased,  material  benefit  followed 
an  operation  performed  by  one  of  us  for  the  relief  of  pan- 
creatitis. Before  the  operation  the  faeces  showed  55.6 
per  cent,  of  "total  fat,"  of  which  51.4  per  cent,  was 
' '  neutral  fat' '  and  4. 2  per  cent.  ' '  fatty  acid. ' '  Six  months 
after  the  operation,  when  the  patient  was  put  on  a  simi- 
lar diet,  there  was  43.0  per  cent,  of  "total  fat,"  of  which 
22,3  per  cent,  was  "neutral  fat"  and  20.7  per  cent,  "fatty 
acid ' ' ;  thus  suggesting  that  the  fat-splitting  process  was 
being  more  efficiently  carried  out,  and  that  a  somewhat 
larger  proportion  of  fat  was  being  absorbed. 

The  utilisation  of  proteids  after  complete  and  partial 
extirpation  of  the  pancreas  has  been  investigated  by 
Abelmann.  He  found  that  when  the  gland  was  com- 
pletely removed  in  dogs,  only  44  per  cent,  of  the  albumin 
given  as  food  was  absorbed,  and  that  when  a  portion  of 
the  organ  was  left  behind,  54  per  cent,  of  the  proteid  was 
made  use  of.  Some  part  of  this  deficient  absorption  he 
ascribed  to  the  presence  of  undigested  fat  in  the  intestinal 
contents.  Administration  of  pigs'  pancreas  to  the  depan- 
creatised  animals  was  found  to  increase  the  amount 
of  utilised  albumin  to  from  74  to  78  per  cent.  De  Renzi 
and  Cavazzani  showed  that  after  extirpation  of  the 
pancreas  the  amount  of  nitrogen  in  the  faeces  was  increased, 
and  Sandmeyer  demonstrated  that  after  partial  extirpa- 
tion of  the  gland  from  62  to  70  per  cent,  of  the  albumin 
of  the  food  was  unused.  Clinically,  Hirschfeld  found 
that  in  certain  cases  of  diabetes,  possibly  due  to  disease 
of  the  pancreas,  as  much  as  31.8  per  cent,  of  the  nitrogen 
of  the  food  reappeared  in  the  faeces,  and  Weintraud  states 
that  in  a  case  of  chronic  pancreatitis,  in  which  the  diag- 
nosis was  confirmed  post-mortem,  45.2  per  cent,  of  the 


2  22       The  Pancreas:  Its  Surgery  and  Pathology 

ingested  proteid  was  found  in  the  stools.  Miiller  re- 
ported that  in  his  cases  the  absorption  of  proteids  was 
only  slightly  affected. 

The   appearance   of  undigested   muscle   fibres   in   the 
stools  has  been  described  by  numerous  observers,  both 
clinically  and   after  partial   or  complete   extirpation  of 
the  pancreas  in  animals.     Fles,  who  was  the  first  to  draw 
attention  to  the  value  of  this  symptom  in  the  diagnosis 
of  pancreatic  disease,  states  that  in  his  case  the  muscle 
fibres    disappeared    after    the    administration    of    calf's 
pancreas.     As  stated  in  the  table  on  page  214,  our  own 
investigations  of  the  faeces    have  shown  that  undigested 
muscle  fibres  can  be  found  more  frequently  in  those  cases 
where  the  functions  of  the  pancreas  are  interfered  with, 
than  in  those  in  which  it  is  apparently  normal,  and  that, 
since  they  were  discovered  in  twenty  out  of  twenty-four 
cases  of  cancer  of  the  pancreas,  but  in  only  sixteen  out  of 
fifty-six  cases  of  simple  pancreatitis,  their  appearance  in 
the  stools,  other  things  being  equal,  indicates  a  serious 
lesion  of  the  gland.     In  some  cases  of  pancreatic  disease, 
undigested  muscle  can  be  detected  in  the  stools  with  the 
naked  eye,  but,  in  the  majority,  they  are  only  found  on 
microscopical   examination.     It  is   impossible,  however, 
to  infer  that  the  functions  of  the  pancreas  are  disturbed 
from  the  appearance  of  muscle  fibres  in  the  faeces  alone, 
for,  excluding  their  presence  from  an  excessive  amount 
of  meat  having  been  taken  in  the  diet,  they  may  also  be 
found  in  cases  where,  owing  to  increased  peristalsis,  or 
putrefactive    changes,    leading    to    secondary    diarrhoea, 
they  are  hurried  through  the  intestine  before  they  have 
had  time  to  be  digested.     Normally  the  stomach  shares 
only  to  a  slight  extent,  according  to  Schmidt,  in  the  disso- 
lution of  muscle,  its  chief  action  being  the  digestion  of 
the  connective  tissue  of  the  meat ;  it  is  probable,  however, 
that  when  the  pancreatic  juice  is  diminished  or  absent, 
gastric  digestion  may  be  continued  lower  down  in  the 


Chemical  Pathology  223 

intestine  than  is  usually  the  case,  and  that  consequently 
proteid  digestion  may  not  be  as  incomplete  as  might  at 
first  sight  be  expected.  On  the  other  hand,  defective 
gastric  secretion  may  lead  to  imperfect  digestion  of  muscle, 
for  the  pancreatic  juice  being  presented  with  more  or  less 
solid  masses  of  fibres,  bound  together  by  connective 
tissue,  can  only  attack  them  slowly  from  the  surface,  in- 
stead of  dealing  quickly  with  separated  cells  or  groups 
of  cells. 

Reduction  or  failure  of  the  pancreatic  secretion  might 
be  expected  to  lead  to  impaired  digestion  of  starchy 
foods  and  the  appearance  of  an  excess  of  carbohydrate 
in  the  stools.  The  observations  made  by  various  inves- 
tigators on  the  faeces,  however,  have  shown  that  only  a 
small  proportion,  or  none  at  all,  of  the  carbohydrate 
taken  in  the  food  is  excreted  unchanged  in  cases  where 
these  conditions  exist.  According  to  Abelmann,  20  to 
40  per  cent,  of  the  amylaceous  material  ingested  reap- 
pears in  the  fasces  in  animals  from  which  the  pancreas 
has  been  extirpated,  while  Mtiller  was  unable  to  find  any 
evidence  that  more  carbohydrate  was  present  in  the  stools 
of  patients  suffering  from  diseases  of  the  pancreas  than  in 
those  of  normal  individuals. 

Our  own  investigations  on  the  faeces  in  pancreatic  dis- 
ease tend  to  support  the  conclusions  of  Miiller,  on  the 
whole ;  for,  although  we  have  found  that  in  some  instances 
a  larger  proportion  of  carbohydrate  than  is  normally 
present  in  the  stools  of  persons  on  a  mixed  diet  could  be 
detected,  this  was  by  no  means  constant,  even  in  well- 
marked  cases.  The  loss  of  weight  and  inability  to  accu- 
mulate fat,  in  spite  of  an  abundant  carbohydrate  diet, 
points,  however,  to  a  diminished  assimilation  in  excess 
of  that  indicated  by  the  condition  of  the  faeces,  and  it  is 
probable  that  the  figures  given  by  analysis  of  the  stools 
cannot  be  taken  as  a  true  index  of  the  loss  to  the  organism 
of  carbohydrate  material.     The  difference  between  the 


224       The  Pancreas:  Its  Surgery  and  Pathology 

amount  assimilated  and  that  present  in  the  stools  is 
probably  to  be  explained  by  bacterial  action,  the  starch 
of  the  food  being  slowly  converted  into  maltose,  and  this 
in  its  turn  being  split  up  into  lactic  acid,  acetic  acid, 
alcohol,  carbon  dioxide,  hydrogen,  etc.,  by  micro-organ- 
isms in  the  intestine.  There  is  thus  a  loss  of  caloric 
potential  which  leads  to  inanition.  The  fact  that  many 
dyspeptics  continue  very  thin,  although  they  take  an 
abundance  of  carbohydrate  food,  is  possibly  to  be  ac- 
counted for,  as  Herter  suggests,  by  a  diminution  in  the 
secretion  of  pancreatic  juice,  and  the  flatulence  of  which 
they  complain  may  also  be  due  to  the  consequent  accumu- 
lation of  carbon  dioxide  and  other  gases,  while  the  drow- 
siness, with  headache  after  meals,  may  arise  partly  from 
the  absorption  of  alcohol  and  various  organic  acids. 

It  seems  likely  that  in  disease  of  the  pancreas  all  the 
three  chief  ferments  usually  suffer  diminution  together, 
but  there  is  reason  to  think  that,  under  some  circum- 
stances, they  are  not  diminished  to  an  equal  degree.  In 
pancreatitis,  due  to  obstruction  or  an  ascending  catarrh  of 
the  ducts,  fat-splitting,  proteolysis,  and  starch-conversion 
are  no  doubt  equally  affected,  but  it  is  said  that  in  fever 
the  ability  to  digest  starches  and  fat  may  be  much  more 
impaired  than  the  capacity  of  the  pancreatic  juice  to  act 
upon  proteids,  an  observation  which  can  only  be  explained 
on  the  assumption  that  trypsin  under  these  circumstances 
is  more  abundantly  secreted  than  the  other  ferments 
(Herter). 

The  stools  in  cases  of  advanced  pancreatic  disease 
generally  present  very  typical  characters;  they  are  fre- 
quent, bulky,  soft,  white,  have  usually  an  acid  reaction 
and  a  peculiar  odour.  Their  bulk  is  partly  to  be  attrib- 
uted to  the  abnormal  quantity  of  undigested  material, 
particularly  fat,  passed  through  the  bowel,  and  partly 
to  the  excessive  fermentation  which  takes  place  in  the 
lower  part  of  the  intestine.     Their  frequency  is  due  in 


Chemical  Pathology  225 

part  to  their  bulk,  and  is  also  no  doubt  contributed  to  by 
the  excess  of  irritating  by-products  they  contain. 

Considerable  difference  of  opinion  exists  as  to  the 
cause  of  the  white  appearance  of  the  fceces  when  the 
pancreatic  secretion  is  much  diminished  or  excluded  from 
the  intestine.  Muller,  as  we  have  seen,  attributes  steat- 
orrhoea  entirely  to  absence  of  bile,  and,  as  it  is  well  known 
that  obstruction  of  the  biliary  passages  gives  rise  to  clay- 
coloured  motions,  he  would  refer  the  absence  of  colour 
also  to  that  cause.  Since  many  cases  of  pancreatic  dis- 
ease in  which  the  typical  white  stools  exist  are  asso- 
ciated with  more  or  less  complete  blocking  of  the  common 
bile-duct  by  gall-stones,  or  growth  in  the  head  of  the 
pancreas,  the  absence  of  bile-pigment  is  without  question 
a  frequent  contributory  factor,  but  that  it  is  not  the 
complete  and  invariable  explanation  there  is  abundant 
evidence  to  show.  We  have  on  several  occasions  met 
with  cases  of  pancreatitis  with  white  stools  where  there 
was  no  jaundice,  and  no  evidence  of  biliary  obstruction 
at  operation,  and  in  which  a  chemical  examination  of  the 
fasces  demonstrated  a  well-marked  reaction  for  sterco- 
bilin.  The  case  already  quoted  on  page  217,  in  which, 
after  cholecystenterostomy,  the  whole  of  the  bile,  which 
had  previously  been  escaping  by  a  fistula,  was  turned 
into  the  small  intestine,  demonstrated  very  clearly  that 
the  presence  of  the  biliary  secretion  is  not  sufficient  to 
ensure  a  return  of  the  normal  colour  when  the  pancreatic 
juice  is  still  absent,  for  the  appearance  of  the  faeces  was 
practically  unchanged  by  the  operation. 

As  far  back  as  1856  Claude  Bernard,  writing  of  dogs 
whose  pancreas  had  been  destroyed,  stated  that  "it  is 
remarkable  that  bile  only  colours  the  faeces  a  very  bright 
yellow,  whilst  with  the  pancreatic  juice  the  bile  takes  a 
very  brown  colour,"  thus  suggesting  that  the  pancreatic 
juice  contributed  indirectly  to  the  colour  of  the  faeces. 
Attention  was  drawn  to  this  observation  thirty-three  years 
15 


2  26       The  Pancreas:  Its  Surgery  and  Pathology 

later  by  T.  J.  Walker,  in  a  paper  read  before  the  Royal 
Medical  and  Chimrgical  Society,  in  which  he  described  two 
cases  of  pancreatic  disease  where  there  were  clay-coloured 
stools,  although  the  liver  and  bile-passages  were  found 
to  be  normal  post-mortem.  He  suggested  that  the  white 
stools,  to  which  he  drew  attention  as  indicative  of  disease 
of  the  pancreas,  depended  for  their  characteristic  appear- 
ance upon  the  absence  of  the  action  of  the  pancreatic 
juice  upon  the  bile-pigment  they  contained.  This  view 
has  been  supported  by  W.  Gordon,  who  reported  a  case  of 
pancreatic  disease,  with  copious  vomiting  of  green  bile, 
in  which  the  motions  were  sometimes  clay-coloured  and 
at  other  times  cream  or  primrose-coloured,  but  never 
brown.  Neither  of  these  observers  produced  any  evi- 
dence, beyond  that  afforded  by  mere  inspection,  that 
stercobilin  was  absent,  or  very  much  diminished,  in  the 
cases  they  report,  nor  did  they  take  into  account  the 
enormous  excess  of  fat  present  in  the  faeces  in  serious  cases 
of  pancreatic  disease.  It  is  to  this  large  excess  of  fat 
that,  in  our  opinion,  the  abnormal  colour  is  chiefly  due. 
The  evidence  on  which  this  opinion  is  based  may  be 
summarised  as  follows :  ( i )  Quantitative  examination  of 
the  stools  from  a  large  number  of  our  cases  has  shown 
that  the  colour  varies  directly  with  the  percentage  of  fat 
present,  the  largest  amount  being  found  in  those  specimens 
which  are  white  to  the  naked  eye,  and  the  least  in  those 
which  approximate  to  the  normal  colour.  (2)  The  glis- 
tening white  appearance  is  most  marked  in  those  speci- 
mens which  are  found  microscopically  to  contain  large 
numbers  of  fatty  acid  crystals,  in  part  probably  for  the 
same  reason  that  snow  and  other  substances  of  a  finely 
crystalline  character  appear  white  in  mass.  (3)  The 
white  stools  on  being  heated  on  the  water-bath  assume  a 
dark  brown  colour.  (4)  Removal  of  the  fat  with  ether 
leaves  a  residue  of  a  dark  brown  colour,  similar  to  that 
obtained    from    normal    fseces.     (5)  Stercobilin    can    be 


Chemical  Pathology  227 

demonstrated  chemically  in  all  specimens  not  derived 
from  patients  in  whom  there  is  complete  obstruction  of 
the  bile-passage  by  cancer  of  the  head  of  the  pancreas, 
gall-stones,  etc.,  the  amount  being  proportional  to  the 
quantity  of  non-fatty  residue.  In  cases  of  pancreatic 
disease  associated  with  incomplete  obstruction  of  the 
biliary  passages  the  amount  of  stercobilin  varies  with  the 
degree  of  obstruction.  (6)  The  white  stools  occasionally 
met  with  in  tuberculosis  of  the  intestine,  and  some  other 
conditions,  where  there  is  defective  absorption  of  fat, 
are  similar  microscopically  and  chemically  to  those  seen 
in  typical  cases  of  pancreatic  disease,  although  there  is  no 
obstruction  to  the  free  flow  of  bile,  and  the  pancreas  is 
not  affected. 

These  considerations  point,  we  think,  to  an  excess  of 
fat  in  the  stools  being  probably  the  most  important 
element  in  the  production  of  the  white  stools  in  seri- 
ous pancreatic  disease.  But  they  do  not  exclude  other 
and  contributory  factors,  and  that  such  exist  is  sug- 
gested by  the  fact  that  when  such  stools  are  exposed 
to  the  air  they  are  .sometimes  seen  to  assume  a  darker 
colour  on  the  surface.  The  acid  reaction  of  the  fseces  in 
many  cases  is  possibly  associated  with  a  modification  of 
the  flora  of  the  intestine,  and  it  appeared  to  us  not  im- 
probable that  this  might  cause  a  partial  or  complete 
reduction  of  the  stercobilin  to  a  colourless  compound 
which,  on  contact  with  the  oxygen  of  the  air,  was  slowly 
converted  into  the  normal  colouring-matter  of  the  stools. 
Experimental  proof  of  this  was  sought  by  taking  a  speci- 
men of  normal,  dark  brown  fseces,  which  had  a  faintly 
acid  reaction,  thoroughly  mixing  it  with  normal  saline, 
so  as  to  form  a  thin  paste,  and  dividing  it  into  two  por- 
tions, which  were  placed  in  sterile  test-tubes  marked  "A" 
and  "B."  The  A-tube  was  plugged  with  wool  and  used 
as  a  control.  To  the  B-tube  was  added,  with  a  sterile 
platinum  wire,  a  minute  fragment  of  fseces  from  a  typical 


228       The  Pancreas:  Its  Surgery  and  Pathology 

white  pancreatic  stool,  and  it  was  then  plugged  with  wool. 
Both  tubes  were  placed  in  the  incubator  and  kept  at  37°  C. 
In  twenty-four  hours  no  change  had  taken  place  in  the 
A-tube,  but  the  lower  part  of  the  contents  of  the  B-tube 
was  distinctly  lighter  in  colour  than  the  upper  portions, 
and  than  the  control.  The  tubes  were  returned  to  the 
incubator  and  examined  daily.  The  control  and  the 
upper  part  of  the  B-tube  gradually  became  slightly 
darker,  but  the  alteration  in  colour  of  the  lower  part  of  the 
latter  previously  noticed  increased  until  the  fourth  day, 
when  it  was  found  to  be  of  a  light  grey-brown  appearance 
and  presented  a  very  marked  contrast  to  the  darker  layers 
above.  No  further  discharge  of  colour  was  observed, 
although  the  experiment  was  continued  for  several  weeks. 

This  result,  incomplete  as  it  was,  pointed  to  the  pres- 
ence in  the  pancreatic  stool  of  organisms  which,  growing 
anaerobically,  caused  changes  in  the  faecal  pigment  that 
resulted  in  partial  decolourisation.  On  repeating  the 
experiment  with  specimens  grown  under  anaerobic  con- 
ditions a  similar  change  was  obtained,  only  that  in  this 
instance  practically  the  whole  of  the  inoculated  tube  was 
affected.  On  spreading  this  light-coloured  material  on  a 
dish,  and  exposing  it  to  the  air,  it  slowly  darkened  and 
assumed  very  much  its  original  appearance.  On  repeat- 
ing the  experiment  with  faeces  of  alkaline  reaction  no- 
alteration  in  colour  could  be  produced. 

The  very  small  proportion  of  fat  in  the  particular  speci- 
men of  fseces  first  submitted  to  experiment  (5.3  per  cent.) 
is  against  the  changes  observed  being  due  to  some  altera- 
tion in  that  constituent,  but  it  will  be  observed  that  we 
were  unable  to  obtain  with  this  specimen  the  dead-white 
appearance  met  with  in  characteristic  cases  of  pancreatic 
disease,  possibly  because  of  the  small  proportion  of  fat 
it  contained.  It  appears  probable,  therefore,  that  the 
characteristic  white  appearance  of  the  stools  met  with  in 
serious  cases  of  pancreatic  disease,  in  which  there  is  no 


Chemical  Pathology  229 

obstruction  of  the  biliary  passages,  is  due  chiefly  to  the 
presence  of  an  excess  of  fat,  particularly  to  the  crystalline 
fatty  acids,  but  partly  also  to  the  reducing  action  of 
bacteria  growing  anaerobically  in  an  acid  medium.  In 
pancreatic  disease  associated  with  biHary  obstruction  the 
absence  of  bile-pigment,  or  its  diminished  amount,  is  also 
no  doubt  a  contributory  factor. 

On  referring  to  the  table  on  page  2 14  it  will  be  seen  that 
in  fifty-eight  of  the  eighty  cases  in  which  there  was  evi- 
dence of  disease  of  the  pancreas  the  fresh  fseces  had  an 
acid  reaction,  while  in  sixteen  they  were  neutral  or  ampho- 
teric to  litmus,  and  in  six  distinctly  alkaline.  The  presence 
or  absence  of  jaundice  appears  to  exert  little  or  no  effect 
upon  the  reaction  of  the  stools  when  the  pancreas  is 
diseased,  for  the  proportion  in  which  they  were  acid  is 
about  the  same  in  jaundiced  and  in  non- jaundiced  patients. 
In  simple  jaundice,  unaccompanied  by  disease  of  the 
pancreas,  and  in  cases  where  there  were  calculi  in  the 
biliary  passages  but  no  bile-pigment  in  the  urine,  on  the 
other  hand,  the  stools  have  generally  been  alkaline  in 
reaction.  This  is  probably  to  be  attributed  to  the  pres- 
ence in  pancreatic  disease  of  free  fatty  acids,  whereas  in 
the  non-pancreatic  cases  the  excess  of  fat  is  due  to  com- 
bined fatty  acids  or  soaps.  The  peculiar  sour  smell  of 
the  white  stools  in  typical  cases  of  diseases  of  the  pancreas 
is  also  due,  in  all  probability,  to  the  higher  free  fatty 
acids  they  contain.  Strasburger  found,  as  a  rule,  a  strik- 
ing diminution  in  the  amount  of  bacteria  contained  in 
icteric  stools,  in  spite  of  the  generally  accepted  view 
that  bile  possesses  antiseptic  properties.  It  is  probable, 
therefore,  that  there  is  a  lessened  rather  than  an  increased 
degree  of  putrefactive  change  in  the  fatty  stools  met  with 
in  such  cases.  Where,  however,  the  amount  of  proteid 
residue  is  at  the  same  time  increased,  as  the  result  of  pan- 
creatic and  intestinal  affections,  putrefaction  may  occur 
and  the  fasces  become  alkaline.     Under  these  conditions 


230       The  Pancreas:  Its  Surgery  and  Pathology 

the  acid  reaction  due  to  the  fatty  acids  may  be  masked 
and  the  feces  be  neutral,  amphoteric,  or  even  alkaline  to 
litmus.  The  association  of  general  enteritis,  including 
chronic  colitis,  with  disease  of  the  pancreas  may  thus 
account  for  the  alkaline  reaction  of  the  stools  met  with 
in  a  few  cases. 

The  hlood  changes  that  result  from  diseases  of  the 
pancreas  have  not,  as  yet,  received  much  attention  from 
investigators,  but  that  they  are  important  and  interesting 
is  shown  by  the  profound  alterations  in  both  its  morpho- 
logical and  chemical  characters  that  are  met  with  in 
serious  and  advanced  lesions,  and  to  a  less  extent  in  milder 
types  of  disease.  The  hsemorrhagic  tendency  in  pancrea- 
titis, to  which  attention  was  drawn  by  one  of  us  in  the 
Hunterian  Lectures  for  1904,  is  an  indication  of  the  altered 
blood  state  induced  by  pancreatic  lesions,  and  the  changes 
in  the  urine  to  which  we  shall  presently  refer,  also  point 
in  the  same  direction. 

Besides  hccmorrhagic  pancreatitis,  and  the  form  of 
local  haemorrhage  to  which  we  have  referred  under  the 
term  "pancreatic  apoplexy,"  there  is  in  many  pancreatic 
affections  a  tendency  to  general  haemorrhage,  and  pa- 
tients often  complain  that  they  very  readily  bruise.  The 
fact  that  this  tendency  is  most  marked  in  cancer  of 
the  head  of  the  pancreas,  and  in  pancreatitis  associated 
with  jaundice,  naturally  suggests  that  it  is  dependent  upon 
the  cholsemia,  but  since  a  haemorrhagic  tendency  is  also 
encountered  in  patients  suffering  from  pancreatitis  un- 
attended by  jaundice,  it  cannot  be  altogether  due  to  that 
cause.  Estimations  of  the  coagulation  time  of  the  blood 
by  one  of  us,  with  Wright's  method,  have  shown  that  it 
may  be  prolonged  in  cases  of  cancer  of  the  head  of  the 
pancreas  to  seven  or  eight  minutes,  or  even  longer,  and 
that  in  pancreatitis  with  deep  jaundice  similar  figures 
may   be    obtained.     In    pancreatitis    without    jaundice, 


Chemical  Pathology  231 

although  the  alteration  is  not  so  marked,  coagulation 
times  of  four  or  five  minutes  are  not  uncommon. 

We  were  at  one  time  disposed  to  think  that  the  explana- 
tion of  the  haemorrhagic  tendency,  and  the  delayed  coagula- 
tion time,  in  pancreatic  disease  might  be  dependent  upon 
the  presence  of  glycerine  in  the  blood  stream,  derived  from 
areas  of  fat  necrosis,  but  we  have  not  been  able  to  ob- 
tain any  experimental  evidence  in  support  of  this  theory, 
either  directly  by  examining  the  blood  or  indirectly  from 
the  urine.  It  is  w^ell  known  that  a  diminution  of  the  lime 
salts  in  the  blood  leads  to  a  tendency  to  haemorrhage,  and 
that  the  haemorrhagic  tendency  in  pancreatic  disease  is 
dependent  on  this  cause  is  highly  probable  for  several 
reasons.  We  have  found  that  the  administration  of  cal- 
cium chloride  to  patients  suffering  from  diseases  of  the 
pancreas  not  only  reduced  the  coagulation  time,  often 
by  several  minutes,  but  is  also  an  efficient  preventive  of 
the  haemorrhage  that  is  liable  to  occur  in  such  cases  during 
and  subsequent  to  operation.  Further,  the  fact  that 
pancreatic  calculi  contain  50  per  cent,  or  more  of  calcium 
salts,  whereas  the  normal  secretion  contains  under  2  per 
cent.,  and  the  presence  also  of  calcium  oxalate  crystals  in 
the  urinary  deposit  of  many  cases  of  pancreatitis,  suggest 
that  inflammation  of  the  gland  is  associated  with  a  dis- 
turbance of  metabolism  which  results  in  an  abnormal 
excretion  of  the  lime  salts  and  a  consequent  improverish- 
ment  of  the  blood. 

There  is  usually  a  diminution  in  the  number  of  erythro- 
cytes in  pancreatitis  which,  in  advanced  and  untreated 
cases,  may  be  very  marked  indeed,  even  when  jaundice 
is  absent.  Thus,  in  one  case  of  chronic  pancreatitis,  in 
which  operation  was  refused,  we  found  3,120,000  red  cells 
per  cubic  millimetre;  nine  months  later  there  were 
1,889,000,  and  three  months  subsequently  1,501,000. 
In  another  case,  where  operation  was  followed  by  rapid 
improvement    there  were  3,472,000  red  cells  per  cubic 


232       The  Pancreas:  Its  Surgery  and  Pathology 

millimetre  before  operation  and  4,634,000  three  weeks 
subsequently. 

In  some  instances,  and  especially  where  the  disease  is 
of  long  standing,  we  have  found  that  the  haemoglobin  has 
not  suffered  a  proportional  decrease  with  the  red  corpuscles, 
and  there  has  consequently  been  a  high  haemoglobin  index, 
similar  to  that  found  in  pernicious  anaemia.  In  one  case 
of  advanced  chronic  pancreatitis,  which  had  previously 
been  diagnosed  as  malaria,  and  in  which  a  floating  biliary 
calculus  was  removed  from  the  common  duct  by  one  of 
us,  a  haemoglobin  index  of  1.4,  with  2,525,000  erythrocytes 
per  cubic  millimetre,  was  found  shortly  after  the  opera- 
tion. Six  months  later  the  haemoglobin  index  was  1.5, 
and  a  blood  count  showed  1,735,000  red  cells  per  cubic 
millimetre.  The  patient  passed  from  under  our  observa- 
tion, but  we  have  heard  that  he  died  shortly  afterwards 
with  all  the  symptoms  of  pernicious  anaemia,  Unfortu- 
nately no  post-mortem  examination  was  made.  Another 
and  similar  case,  where  a  haemoglobin  index  of  1.5  and  a 
red  blood  count  of  1,293,000  were  obtained,  was  examined 
after  death,  and  the  pancreas  found  to  be  small,  hard, 
and  cirrhosed.  These  cases  suggest  that  in  some  in- 
stances inflammatory  changes  in  the  pancreas  are  liable 
to  be  associated  with  alterations  in  the  blood,  similar 
to  those  met  with  in  so-called  idiopathic  pernicious 
anaemia,  and  that  in  making  a  prognosis  in  cases  of  pan- 
creatitis the  condition  of  the  blood  must  be  considered. 

In  our  experience  it  is  rare  to  meet  with  a  well-marked 
leucocytosis  in  diseases  of  the  pancreas,  but  up  to  the 
present  our  observations  have  been  limited  to  cases  of 
chronic  pancreatitis  and  cancer  of  the  gland.  So  far  we 
have  not  had  the  opportunity  of  examining  the  condition 
of  the  blood  in  acute  inflammation,  but  Woolsey  in  three 
cases  of  acute  pancreatitis  obtained  leucocyte  counts  of 
39,000,  17,600,  and  26,000  per  cubic  millimetre  respec- 
tively. 


Chemical  Pathology  233 

The  changes  met  with  in  the  urine  in  diseases  of  the 
pancreas  arise  in  part  from  the  altered  conditions  existing 
in  the  intestinal  tract,  and  in  part  from  perverted  metab- 
olism and  excessive  tissue  waste. 

Ethereal  Sulphates  and  Indican. — Since  a  reduced  se- 
cretion of  pancreatic  juice  is  followed  by  an  impaired 
digestion    of    proteids,    and    these,    as   we    have    seen, 
are  likely  to  be  attacked  and  broken  down  by  bacteria, 
it  might  be    expected    that    the   urine   would   in    such 
cases    show    signs   of    excessive   intestinal   putrefaction, 
in  the  shape  of  an  increased  excretion  of  ethereal  sul- 
phates and  a  pathological  excess  of  indican.     According 
to  Herter,  this  does  in  fact  occur,  for  he  states  that  when 
both  the  bile  and  pancreatic  secretion  are  completely 
excluded  from  the  intestine  there  is  an  excess  of  indican 
and  the  ethereal  sulphates  are  always  very  largely  in- 
creased, the  proportion  to  preformed  sulphates  rising  to 
I  :  6,  or  I  :  4,  or  even  i  :  i,  as  compared  with  the  normal 
of  about   I  :  10.     Edsall,  on  the  other  hand,  considers 
that  a  diminution  in  the  amount  of  ethereal  sulphates 
in  the  urine  is  an  indication  of  pancreatic  disease,  for  he 
points  out  that,   although  the  products   of  proteolytic 
digestion  are  readily  decomposed  by  bacteria,  the  native 
albumins   are  not.     If,   therefore,   there  is  little  or  no 
proteolytic  digestion  going  on  in  the  intestine,  as  is  the 
case  in  severe  lesions  of  the  pancreas,  the  products  of 
bacterial  activity  will  be  lessened  and  the  quantity  of 
ethereal  sulphates  and  indican  in  the  urine  decreased. 
Pisenti  has  estimated  the  amount  of  indican  in  the  urine 
of  dogs  before  and  after  tying  the  pancreatic  duct.     In 
one  instance  he  found  11.70  to  19.90  mg.  and  in  another 
1 5.0  to  2 1. o  mg.  per  day,  before  the  operation,  as  compared 
with  4.30  to  4.20  mg.,  and  6.0  to  9.0  mg.,  per  day,  respec- 
tively, after  ligature,  thus  showing  a  marked  diminution. 
The  administration  of  pancreas-peptone  to  animals   in 
which  the  duct  had  been  tied  he  found  increased  the 


234       The  Pancreas:  Its  Surgery  and  Pathology 

quantity  of  indican  excreted.  In  1886  Gerhardi  reported 
a  case  of  pancreatic  disease  which  he  had  successfully 
diagnosed  during  life  from  the  absence  of  indicanuria, 
when  the  clinical  symptoms  suggested  obstruction  of  the 
upper  part  of  the  intestine.  Absence  of  indicanuria  has 
also  been  observed  by  Stefanani  in  a  case  of  purulent 
pancreatitis,  and  by  Biondi  in  a  case  of  adenoma  of  the 
pancreas.  The  question  has  been  carefully  investigated 
by  Katz  in  depancreatised  dogs.  He  states  that  when 
the  animals  were  fed  with  easily  digested  and  rapidly 
absorbed  food,  the  excretion  of  ethereal  sulphates  was 
low — 0.032,  0.022,  0.069  gram  daily;  but  that  when  a 
diet  of  pure  meat  was  substituted  the  daily  excretion  was 
unusually  high— 0.076,  0.089  gram,  although  readings 
as  low  as  0.024  were  sometimes  obtained  even  under  these 
conditions.  He  also  failed  to  detect  any  diminution  in 
the  amount  of  indican  after  lesions  of  the  pancreas;  in 
fact,  in  many  instances  there  was  marked  indicanuria. 
On  a  pure  meat  and  milk  diet  he  found  that  there  was  an 
abundance  of  indican  in  the  urine,  the  amount  being 
greater,  and  its  increase  distinctly  marked,  on  the  day 
following  the  attack,  especially  in  those  cases  where  the 
animals  took  no  nourishment  after  the  operation,  and  even 
when  they  died  quickly  from  duodenal  necrosis.  In 
those  animals  which  long  survived  the  operation  no  dim- 
inution in  the  excretion  of  indican  was  observed.  Similar 
results  have  also  been  obtained  by  de  Renzi.  Schlagen- 
haufer  records  an  increase  of  indican  in  a  case  of  syphilitic 
interstitial  pancreatitis  that  he  investigated,  and  Hen- 
nige  has  referred  the  indicanuria  found  in  cholera  and 
lead-colic  .  to  an  alteration  in  the  pancreatic  secretion 
caused  by  nervous  influences. 

Our  own  investigations  of  the  relation  between  the 
preformed  and  ethereal  sulphates  in  cases  of  pancreatic 
disease  have  given  such  varied  results  that  we  have  come 
to  the  conclusion  that  they  are  due  to  factors  which  have 


Chemical  Pathology  235. 

no  direct  relation  to  the  activities  of  the  gland.  Simi- 
larly, although  we  have  found  an  excess  of  indican  in  49 
per  cent,  of  our  cases  of  chronic  pancreatitis  and  in  54 
per  cent,  of  cancer  cases,  there  has  been  no  relation  be- 
tween the  intensity  of  the  lesion  and  the  degree  of  indi- 
canuria.  The  truth  appears  to  be  that,  although  absence 
or  a  diminished  secretion  of  pancreatic  juice  provides 
conditions  under  which  there  may  be  an  abnormal  pro- 
duction of  aromatic  derivatives  in  the  intestine,  these  do 
not  make  their  appearance  in  the  urine  unless  there  is  at 
the  same  time  some  affection  of  the  intestinal  wall  which 
facilitates  absorption,  and  we  have  therefore  come  to 
look  upon  an  excess  of  indican  and  ethereal  sulphates  in 
the  urine  in  pancreatic  diseases  as  an  indication  of  an 
associated  enteritis. 

Bile. — Owing  to  the  anatomical  relations  of  the  common 
bile-duct,  the  duct  of  Wirsung,  and  the  head  of  the  pan- 
creas, circumstances  which  interfere  with  the  free  flow  of 
the  pancreatic  secretion  into  the  intestine  are,  in  many 
cases,  likely  to  obstruct  the  passage  of  bile  at  the  same 
time,  giving  rise  to  jaundice  and  the  appearance  of  bile 
in  the  urine.  Hence  the  urine  in  diseases  of  the  pancreas 
is  frequently  of  a  deep  yellow  or  brown  colour,  and  gives 
a  reaction  for  bile-pigment.  Bilious  urine  and  jaundice 
are,  however,  by  no  means  constantly  found  in  diseases 
of  the  pancreas,  even  in  pancreatitis  associated  with 
gall-stones  in  the  lower  part  of  the  common  bile-duct. 
Bile-pigment  has  been  detected  in  the  urine  in  62  per 
cent,  of  our  cases  of  chronic  pancreatitis  associated  with 
cholelithiasis,  and  in  only  16  per  cent,  of  those  in  which  no 
biliary  calculi  could  be  found  in  the  common  duct  at  the 
time  of  operation.  Bile-pigment,  in  large  amounts,  was 
present  in  the  urine  of  all  the  twenty-four  cases  of  malig- 
nant disease  of  the  pancreas  included  in  the  list  on  page 
214. 

The  relation  of  urobilin  to  the  bile-pigments  has  been  the 


236       The  Pancreas:  Its  Surgery  and  Pathology 

subject  of  much  controversy,  but  it  is  now  generally 
accepted  that  if  the  bile  is  completely  shut  off  from  the 
intestine  no  urobilin  can  be  found  in  the  urine.  The  fact 
that  the  urine  of  only  three  of  the  above  mentioned  cases 
of  malignant  disease  gave  a  reaction  for  urobilin  is  interest- 
ing in  this  connection,  for  they  were  the  only  three  in 
which  stercobilin  could  be  found  in  the  faeces.  A  patho- 
logical excess  of  urobilin  was  present  in  61  per  cent,  of 
our  cases  of  chronic  pancreatitis  with  an  obstruction  of 
the  common  bile-duct,  and  in  40  per  cent,  of  those  in 
which  no  obstruction  existed  at  the  time  of  operation. 
The  urobilinuria  coexisted  with  jaundice,  and  the  presence 
of  bile-pigment  in  the  urine,  in  43  per  cent,  of  the  former, 
but  in  only  6  per  cent,  of  the  latter. 

Azoturia. — Disturbances  of  intestinal  digestion  are  said 
frequently  to  give  rise  to  an  increased  excretion  of  nitro- 
genous compounds  in  the  urine,  but  as  the  increase  appears 
to  be  closely  related  to  excessive  putrefactive  changes  in 
the  intestine,  and,  as  we  have  seen,  these  are  not  by  any 
means  a  constant  accompaniment  of  diseases  of  the  pan- 
creas, no  constant  variation  from  the  normal  in  this 
respect  can  be  looked  for.  Azoturia  is  well  known  to 
occur  in  diabetes,  and  it  has  been  observed,  without 
glycosuria,  by  de  Dominicus,  Hedon,  and  Thiroloix  after 
extirpation  of  the  pancreas  in  animals.  The  excess  is 
here,  however,  probably  due  to  abnormal  tissue  destruc- 
tion, for  it  is  not  met  with  after  partial  extirpation  of  the 
gland  and  is  associated  with  a  constant  dextrose-nitrogen 
ratio.  In  most  of  our  cases  of  pancreatitis  the  excretion 
of  urea  has  not  been  excessive,  the  uric  acid  has  varied 
little  from  the  normal,  and  the  total  nitrogen,  in  the 
few  cases  in  which  we  have  estimated  it,  has  fallen  within 
normal  limits.  In  cancer  of  the  pancreas  we  have  usually 
found  that  there  was  a  subnormal  proportion  of  urea. 

The  excretion  of  phosphates  is  said  to  be  increased  by 
disease  of  the  pancreas,  and  de  Dominicus  states  that 


Chemical  Pathology  237 

an  increase  of  phosphoric  acid  is  characteristic  of  pancre- 
atic lesions,  even  in  those  cases  where  there  is  no  glyco- 
suria. But  since  the  chief  source  of  the  phosphoric  acid 
in  the  urine  is  the  food,  the  nature  of  this  will  largely 
control  the  output.  Thus  David  Young,  experimenting 
with  the  case  of  pancreatic  infantilism  reported  by 
Byrom  Bramwell,  found  that  when  the  patient  was  taking 
a  milk  diet  the  amount  of  phosphoric  acid  was  extremely 
small,  but  that  during  the  administration  of  pancreatic 
extract  the  quantity  underwent  a  very  marked  and  rapid 
increase.  The  explanation  he  offers  is  that  the  caseino- 
gen  of  the  milk  was  the  source  of  the  phosphorus  in  the 
urine.  In  the  stomach  it  was  broken  up  into  paranuclein, 
containing  4  per  cent .  of  phosphorus ,  and  a  proteid .  Para- 
nuclein itself  is  insoluble,  but  when  it  is  acted  upon  by 
the  alkaline  pancreatic  secretion  it  is  dissolved  and  split 
into  paranucleic  acid  and  an  albumose,  from  which  the 
phosphoric  acid  of  the  urine  was  derived.  We  have  been 
unable  to  detect  any  marked  variation  from  the  normal 
as  regards  the  excretion  of  phosphates  in  any  of  our  cases, 
and  cannot  confirm  the  statement  of  de  Dominicus  or  the 
observation  of  Young,  although  with  regard  to  the  latter 
our  investigations  have  been  limited  to  two  cases  of 
malignant  disease  of  the  pancreas. 

The  excretion  of  chlorides  in  our  cases  of  pancreatitis 
has  not,  as  a  rule,  been  noticeably  disturbed,  but  we  have 
found  that  in  cancer  of  the  pancreas  the  output  has  been 
frequently  subnormal,  possibly  owing  to  the  presence  of 
pathological  exudates. 

Acetone  Bodies. — Among  the  effects  produced  by  extir- 
pation of  the  pancreas  in  animals  is  the  appearance  of 
acetone,  diacetic  acid,  and,  occasionally,  /^-oxybutyric 
acid  in  the  urine.  Thus  Baldi  found  1.043  grams  of 
acetone  on  the  second  day  after  the  operation,  0.652  gram 
on  the  third  day,  and  later  0.385  gram,  0.282  gram,  and 
0.049  gram,  as  compared  with  the  normal  of  0.0  gram  to 


238       The  Pancreas:  Its  Surgery  and  Pathology 

0.105  gram.  Minkowski  observed  that  the  excretion  of 
these  substances  was  most  marked  when  the  animals  ex- 
perimented upon  became  emaciated,  and  that  the  largest 
amounts  of  /?-oxybutyric  acid  were  found  when  the  quan- 
tity of  sugar  was  diminishing  in  the  later  stages  of  the 
disease. 

Acetone  and  diacetic  acid  have  been  found  in  the 
urine  in  four  out  of  the  five  cases  of  acute  pancreatitis 
in  which  we  have  had  the  opportunity  of  investigating 
the  urine,  in  29  per  cent,  of  our  cases  of  chronic  pancrea- 
titis, and  in  31  per  cent,  of  the  cases  in  which  there  was  a 
malignant  growth  of  the  pancreas.  The  cases  of  chronic 
inflammation  in  which  these  substances  were  found  were 
all  of  some  standing  and  showed  evidence  of  consider- 
able tissue  wasting.  In  one  case  where  the  pancreatitis 
had  followed  typhoid  fever,  and  the  patient  was  in  an 
extremely  serious  condition  when  she  came  under  our 
observation,  the  urine  contained  enormous  quantities  of 
both  acetone  and  diacetic  acid.  Three  days  after  opera- 
tion the  urine  was  again  examined,  and  acetone  bodies 
were  found  to  be  still  present  in  very  large  amounts. 
As  the  patient  was  becoming  comatose  and  her  condition 
was  serious,  she  was  injected  intravenously  with  three 
pints  of  normal  saline  solution.  This  caused  a  temporary 
increase  in  the  excretion  of  the  acetone  bodies,  but  in 
about  seventy-two  hours  they  began  to  diminish,  and  six 
days  after  the  injection  they  could  no  longer  be  detected. 
The  patient's  appetite  and  general  condition  improved 
at  the  same  time,  and  she  eventually  made  a  complete 
recovery. 

The  source  of  the  acetone  bodies,  both  in  wasting 
conditions  and  diabetes,  has  been  much  debated.  It 
would  appear  that  they  are  formed  within  the  system 
and  not  in  the  intestinal  tract,  for  the  administration  of 
purgatives  does  not  diminish  the  quantity  of  acetone  ex- 
creted in  the  urine ;    indeed,  according  to  von  Noorden, 


Chemical  Pathology  239 

it  may  occasionally  cause  an  increase.  The  carbohy- 
drates were  at  one  time  looked  upon  as  the  material  from 
which  they  originated,  but  this  view  was  discarded,  and 
it  was  then  supposed  that  they  were  formed  in  the  process 
of  disintegration  of  proteids.  More  recently  attention 
has  been  turned  to  the  fats,  since  /5-oxybutyric  acid 
and  its  derivatives,  acetone  and  diacetic  acid,  can  be 
derived  from  some  fats  by  a  simple  chemical  process, 
and  at  the  present  time  this  theory  has  the  largest  num- 
ber of  supporters.  It  is  also  possible,  however,  that  they 
may  arise  synthetically  within  the  body  from  simple 
carbon  derivatives  resulting  from  the  breaking  down 
of  carbohydrates,  proteids,  and  fats,  and  that  this  is  a 
probable  explanation  is  suggested  by  the  conditions 
under  which  they  may  make  their  appearance  in  the  urine 
and  the  circumstances  that  have  been  found  to  control 
the  quantities  excreted. 

Calcium  Oxalate. — In  examining  the  urine  from  cases  of 
pancreatic  disease  we  were  early  struck  by  the  frequent 
occurrence  of  well-marked  deposits  of  calcium  oxalate 
crystals  in  many  of  them.  Further  experience,  now 
extending  to  some  five  hundred  examinations,  has 
only  served  to  emphasise  this  early  observation,  and 
to  suggest  that  there  is  probably  a  connection  between 
chronic  inflammatory  lesions  of  the  pancreas  and  oxal- 
uria.  Microscopical  examination  of  the  centrifugalised 
deposit  from  the  urine  has  shown  that  oxalate  crystals 
were  present  in  63  per  cent,  of  our  cases  of  chronic  pan- 
creatitis, or  in  73  per  cent,  if  those  in  which  the  urine 
contained  bile-pigment  be  excluded.  The  crystals  are 
generally  numerous  and  are  frequently  very  small,  so  that 
their  nature  can  sometimes  be  only  recognised  by  examin- 
ing them  with  high  powers  of  the  microscope  and  by  their 
chemical  reactions.  Quantitative  examination  in  five 
cases  has  shown  that  the  urine  contained  an  actual  excess 
of  oxalic  acid,  and  that  the  deposit  was  not  merely  caused 


240       The  Pancreas:  Its  Surgery  and  Pathology 

by  physical  conditions.  Thus  in  one  instance  the  output 
for  twenty-four  hours  was  found  to  be  0.03  gram,  and  in 
another  0.037  gram .  We  have  not  observed  this  condition 
in  acute  pancreatitis  and  rarely  in  cancer  of  the  pancreas. 
Its  association  with  chronic  pancreatitis  is  interesting  in 
view  of  the  fact  that  a  similar  deposit  of  oxalate  crys- 
tals is  not  infrequently  met  with  in  diabetes,  and  that  a 
diminution  in  the  output  of  sugar  in  this  disease  is  accom- 
panied by  an  increase  in  the  oxalate  deposit  (vicarious 
oxaluria) .  Diabetes  has  also  been  noticed  occasionally  to 
follow  long-continued  oxaluria.  Experimenting  on  dogs, 
J.  Scott  found  that  potassium  oxalate  was  a  depressing 
drug  and  that  large  doses  increased  nitrogenous  metabol- 
ism, but  he  was  unable  to  induce  glycosuria  by  the  subcu- 
taneous injection  of  from  0.25  to  0.75  gram. 

The  origin  of  the  oxalic  acid  in  the  urine  is  disputed. 
Part,  no  doubt,  is  directly  derived  from  the  food,  but  part 
probably  arises  from  the  breaking  down  of  purin  bodies 
within  the  organism.  The  experiments  of  Helen  Baldwin 
show  that,  in  dogs,  the  excretion  of  oxalates  is  increased 
by  the  administration  of  cane-sugar  and  glucose  for  long 
periods.  Herter  attributes  this  to  the  excessive  fermenta- 
tion and  induced  gastritis,  but,  since  Ssobolew  has  shown 
that  overfeeding  animals  with  carbohydrates  gives  rise  to 
changes  in  the  islands  of  Langerhans,  it  is  not  improbable 
that  the  oxaluria  found  in  these  experiments,  and  in 
chronic  pancreatitis,  may  be  due  to  a  disturbance  of 
metabolism  arising  from  changes  in  the  functions  of  the 
cell  islets. 

Carbohydrates. — The  alterations  in  the  urine  that  we 
have  so  far  considered,  although  sufficiently  striking  in 
many  instances,  are  not  peculiar  to  diseases  of  the  pan- 
creas .  They  probably  result  directly  or  indirectly  from  the 
disturbances  of  digestion,  or  from  alterations  of  internal 
metabolism,  to  which  the  pancreatic  lesions  give  rise,  but 
they  may  also  be  brought  about  by  other  and  quite  distinct 


Chemical  Pathology  241 

causes.  So  far  as  experimental  research  goes,  however,  the 
appearance  of  certain  carbohydrates  in  the  urine  is  directly 
and  peculiarly  the  result  of  a  failure  on  the  part  of  the 
pancreas  to  perform  its  functions  in  the  internal  economy 
of  the  body.  The  question  of  pancreatic  diabetes  will  be 
fully  considered  in  a  subsequent  chapter,  so  that  it  will 
be  sufficient  to  mention  here  that  extirpation  of  the  pan- 
creas in  animals  has  been  shown  to  give  rise  to  the  ap- 
pearance of  dextrose  in  the  urine,  and  that  more  or  less 
profound  changes  in  the  structure  of  the  gland  have  been 
met  with  in  many  cases  of  human  diabetes. 

In  addition  to  dextrose,  however,  other  sugars  have  been 
described  as  present  in  the  urine  in  a  few  cases  of  pancreatic 
disease.  Le  Nobel  has  described  a  case  of  glycosuria  with 
fatty  stools,  in  which  there  w^as  a  reducing  substance  in 
the  urine  having  the  characters  of  maltose.  Von  Ackeron 
found  a  similar  substance  in  a  case  of  pancreatic  carci- 
noma. Rosenheimhas  recorded  a  case  of  maltosuria,  w4th 
steatorrhoea  and  considerable  loss  of  w^eight,  in  which 
interstitial  pancreatitis  w^as  found  post-mortem.  A 
similar  case  has  also  been  reported  by  Lepine.  In  an 
examination  of  two  hundred  and  forty-five  specimens  of 
urine  from  cases  of  pancreatic  disease  by  the  phenylhy- 
drazin  test,  we  met  with  two  in  which  an  osazone  having 
the  characters  of  maltosazone  was  obtained  in  sufficient 
quantities  for  a  careful  examination,  and  five  in  which  a 
small  deposit  of  crystals,  probably  also  maltosazone,  was 
given.  One  of  the  former  was  a  patient  on  whom  an 
operation  for  stone  in  the  common  bile-duct  had  been 
performed  five  years  previously.  Maltosuria  is  thus  a 
rare  condition,  and  it  is  doubtful  how  far  it  is  directly 
dependent  upon  disease  of  the  pancreas. 

Attention  was  first  directed  to  the  occurrence  of  pen- 
tosuria by  the  observations  of  Salkowski  and  Jastrowitz, 
who  discovered  a  pentose  in  the  urine  of  a  morphine-eater, 
with  temporary  glycosuria,  in  1892.  Previous  to  this 
16 


242       The  Pancreas:  Its  Surgery  and  Pathology 

observation  pentoses  had  been  met  with  only  in  plants, 
and  it  was  believed  that  the  animal  organism  was  incapa- 
ble of  building  them  up.  Subsequently  two  cases  of  pure 
pentosuria,  without  any  dextrose,  were  described  by  Sal- 
kowski  and  Blumenthal.  The  excretion  of  pentose  in 
these  cases  was  found  to  be  independent  of  the  diet,  and 
did  not  in  any  way  affect  the  general  condition  of  the 
patients.  A  diminution  of  the  amount  of  indican  was 
observed  in  both.  On  this  account,  but  more  particu- 
larly because  the  osazone  obtained  from  the  urine  ap- 
peared to  be  identical  in  its  appearance,  melting-point, 
and  solubilities  with  that  obtainable  from  the  pancreas, 
Salkowski  assumed  that  the  pentosuria  was  dependent 
upon  an  abnormally  increased  formation  and  destruction 
of  the  nucleo-proteid  of  that  organ.  This  assumption 
derived  support  from  the  observations  of  Kulz  and  Vogel, 
who  found  that  a  pentose  could  be  detected  in  the  urine 
of  starving  dogs  after  removal  of  the  pancreas.  They 
also  examined  the  urine  of  eighty  diabetics  and  found  a 
well-marked  pentose  reaction  in  sixty-four,  in  twelve  the 
test  gave  doubtful  results,  and  in  four  no  reaction  could 
be  obtained.  Salkowski  and  Blumenthal,  however,  were 
unable  to  detect  any  pentose  in  ten  diabetics  whose  urine 
they  carefully  examined,  and  in  none  of  the  cases  of  in- 
flammatory or  malignant  disease  of  the  pancreas  that  we 
have  investigated  has  any  evidence  of  the  presence  of  a 
pentose  been  found.  Although  Salkowski  regarded  pen- 
tosuria as  an  important  indication  of  pancreatic  disease, 
it  is  so  rarely  met  with  that  it  is  of  little  practical  value, 
and  apart  from  the  evidence  already  quoted,  there  is  no 
proof  that  when  present  it  is  dependent  upon  lesions  of 
the  gland.  It  has  also  to  be  remembered  that  minimal 
traces  of  pentose  may  be  met  with  after  the  ingestion  of 
large  quantities  of  plums,  cherries,  bilberries,  and  other 
substances  comparatively  rich  in  that  variety  of  sugar. 
The  pentose  excreted  under  these  conditions  is,  however. 


Chemical  Pathology  243 

the  dextrorotatory  form,  whereas  that  met  with  in  chronic 
pentosuria,  of  which  a  few  cases  have  since  been  reported, 
is  optically  inactive. 

The  ''Pancreatic''  Reaction  (Cammtdge). — Although  it 
cannot  be  considered  as  proved  that  the  presence  of  a 
pentose  in  the  urine  is  dependent  upon  disease  of  the 
pancreas,  the  results  of  the  investigations  that  we  have 
been  carrying  out  since  the  early  part  of  the  year  1901 
suggest  that,  in  inflammatory  lesions  of  the  gland, 
there  is  excreted  by  the  kidneys  a  substance  which, 
on  hydrolysis,  yields  a  body  giving  the  reactions  of  a 
pentose.  The  initial  stages  of  these  investigations  were 
referred  to  and  described  in  our  Hunterian,  and  Arris  and 
Gale  lectures,  delivered  at  the  Royal  College  of  Surgeons 
in  1904,  and  the  results  of  further  research  were  embodied 
in  a  paper  read  by  one  of  us  before  the  Royal  Medical 
and  Chirurgical  Society  in  March,  1906. 

The  most  striking  indication  of  inflammatory  lesions 
of  the  pancreas  is  undoubtedly  furnished  by  the  dis- 
covery of  fat  necrosis,  either  during  life  or  post-mortem. 
This  condition  is  most  characteristically  met  with  in  acute 
and  gangrenous  pancreatitis,  but  it  is  not  uncommon  to 
find  less  marked  changes  in  chronic  inflammation  of  the 
gland,  and  it  appeared  to  us  possible  that,  even  in  those 
cases  of  chronic  pancreatitis  where  no  visual  evidence 
existed  of  the  fat-splitting  process,  there  might  still  be 
molecular  changes  whigh  could  be  recognized  by  the 
alterations  produced  in  the  chemical  composition  of  the 
blood.  The  hemorrhagic  tendency  we  had  noticed,  and 
the  microscopical  changes  found  in  the  blood  of  patients 
suffering  from  diseases  of  the  pancreas,  pointed  to  there 
being  some  connection  between  the  two  conditions,  and, 
bearing  in  mind  the  effects  produced  in  animals  by  the 
subcutaneous  injection  of  glycerine,  it  occurred  to  us 
that  in  man  the  continued  action  of  minute  doses,  such 


( 


244       The  Pancreas:  Its  Surgery  and  Pathology 

as  fat  necrosis  would  give  rise  to,  might  produce  such  a 
blood  state  as  these  patients  exhibited. 

Starting  on  the  theory  that  there  was  some  such  con- 
nection between  fat  necrosis  and  the  blood  state  found  in 
pancreatic  disease,  we  commenced  our  investigations  by 
examining  the  blood  of  several  cases  of  pancreatitis  for 
glycerine  and  glycerine  derivatives.  But,  as  we  quickly 
realised  that  such  direct  proof  was  not  practicable,  owing 
to  the  small  amounts  of  blood  available  at  the  bedside, 
and  to  the  relatively  small  quantity  of  glycerine  likely 
to  be  present  in  it,  we  turned  our  attention  to  the  urine, 
in  the  hope  of  finding  indirect  evidence  in  favour  of  our 
hypothesis.  The  well-known  selective  power  of  the  kid- 
neys, by  which  they  detect  and  pick  out  abnormal  constit- 
uents of  the  blood,  favoured  the  view  that  the  soluble 
products  of  fat  necrosis,  or  their  derivatives,  might  cause 
changes  in  the  urine  which,  from  the  large  bulk  of  material 
readily  available  for  examination,  could  be  satisfactorily 
detected.  It  is  well  known  that  glycerine  on  being  boiled 
with  nitric  acid  gives  rise  to  glycerose,  which  can  be 
recognised  by  the  osazone  that  it  forms  with  phenylhy- 
drazin.  When  this  test  was  applied  to  the  urine  from 
known  cases  of  pancreatitis,  the  appearance  of  a  much 
more  marked  deposit  of  crystals  than  was  obtained  from 
normal  and  most  pathological  specimens  seemed  at  first 
sight  to  lend  support  to  our  theory,  but  as  subsequent 
investigations  showed  that  other  mineral  acids  gave 
similar  results,  and  it  was  found  that  the  precipitate  had 
not  the  characters  of  glycerosazone,  it  became  necessary 
to  look  for  some  other  explanation  of  the  different  be- 
haviour of  the  urine  from  pancreatic  and  non-pancreatic 
cases. 

Since  comparative  tests  proved  that  cleaner  and  more 
satisfactory  preparations  could  be  obtained  with  hydro- 
chloric than  with  nitric  or  sulphuric  acid,  it  was  adopted 
for  routine  work  and  the  original  nitric  acid  method  aban- 


Chemical  Pathology  245 

doned.  The  procedure  we  made  use  of  for  our  clinical 
investigations  has  been  described  under  the  term  "the 
A-reaction,"  and  was  carried  out  as  follows: 

A  specimen  of  the  urine  to  be  examined  was  carefully  fil- 
tered, and  10  c.c.  of  the  filtrate  poured  into  a  small  flask. 
One  cubic  centimetre  of  strong  hydrochloric  acid  (sp.  gr. 
1. 16)  was  added,  and,  a  small  funnel  having  been  placed 
in  the  neck  of  the  flask  to  act  as  a  condenser,  it  was 
placed   on    a    sand-bath   and 
gently  boiled  for  from  five  to 
ten    minutes,   after  the    first 
sign  of  ebullition  was  detected 
(Fig.  97).     A  mixture  of  5  c.c. 
of  the  filtered  urine  and  5  c.c. 
of    distilled   water  was   then 
poured  into  the  flask,  which 
was  afterwards  well  cooled  in 
running  water.     The  excess  of 
acid  was  now  neutralised  by 
slowly  adding  4  grams  of  lead 
carbonate,  and,  after  standing 
for  a  few  minutes  to  allow  of 
the  completion  of  the  reac- 
tion, the  flask  was  cooled  in 
water  to  the  lowest  possible 
temperature,  and  the  precipi- 
tate removed  by  careful  filtra- 
tion through  a  well-moistened, 
close-grained  filter-paper.      The   clear   filtrate  was  then 
made  up  to  15  c.c,   and  added  to  2  grams  of  powdered 
sodium  acetate,  0.75  gram  of  phenylhydrazin  hydrochlor- 
ate,  and  i  c.c.  of  50  per  cent,  acetic  acid  contained  in  a 
small  flask  fitted  with  a  funnel-condenser.     The  mixture 
was  gently  boiled  on  a  sand-bath  for  five  minutes,  poured 
into  a  test-tube,  made  up  to  15  c.c,  and  allowed  to  cool 
undisturbed.     After  a  period,  varying  with  the  severity 


Fig.  97. — "Pancreatic"  re- 
action flasks  fitted  with  fun- 
nel condensers  on  a  sand-bath. 


246       The  Pancreas:  Its  Surgery  and  Pathology 


of  the  case,  of  from  one  to  twenty-: 


Fig.  98. — "Pancreatic"  reaction-crys- 
tals, prepared  by  the  A-method;  from 
a  case  of  acute  pancreatitis  (X   192). 


Fig.  99. — "Pancreatic"  reaction-crys- 
tals, prepared  by  the  A-method;  from  a  case 
of  chronic  pancreatitis  due  to  the  presence 
of  a  gall-stone  in  the  pancreatic  portion  of 
the  common  bile-duct  (X  192). 


four  hours,  a  more  or 
less  abundant  floc- 
culent  yellow  pre- 
cipitate, occupying 
a  quarter  or  more 
of  the  test-tube, 
was  seen  to  have 
formed,  and  this, 
when  examined  un- 
der the  microscope 
with  a  -g-inch  objec- 
tive, was  found  to 
consist  of  sheaves 
and  rosettes  of 
golden  yellow  crys- 
tals. The  deposit 
met  with  in  non- 
pancreatic urines 
was  usually  much 
less  abundant,  and 
had  not,  as  a  rule, 
the  light  fiocculent 
appearance  of  that 
obtained  in  speci- 
mens from  well- 
marked  cases  of 
pancreatitis. 

Comparison  of  the 
crystals  from  differ- 
ent cases  showed 
that  they  were  not 
always  of  the  same 
type,  and  experi- 
ments indicated 
that  there  was  also 
a  difference  in  their 


Chemical  Pathology 


247 


Fig.  100. — "Pancreatic"  reaction- 
crystals,  prepared  by  the  A-reaction; 
from  a  case  of  malignant  disease  of  the 
pancreas  (X   192). 


solubilities.  The  crystals  fjom  cases  of  acute  and  sub- 
acute pancreatitis 
were  found  to  be 
fine,  slender,  and 
hair -like  in  form, 
and  on  being  irri- 
gated with  7,7,  per 
cent,  sulphuric  acid 
under  the  microscope 
were  observed  to  dis- 
appear in  under  half 
a  minute  after  the 
acid  first  touched 
them,  taking  the 
average  of  three  or 
more  determinations. 
In  malignant  disease, 
on  the  other  hand, 
the  more  typical 
crystals  were  broad, 
coarse,  and  sword- 
like, and  took  from 
three  to  five  minutes 
to  dissolve  in  33  per 
cent,  sulphuric  acid. 
Those  from  cases  of 
chronic  pancreatitis, 
and  most  non-pan- 
creatic diseases,  were 
intermediate  in  form 
and  rate  of  solution, 
dissolving  in  dilute 
sulphuric  acid  in 
from  one  to  two  min- 
utes after  the  acid  first  reached  them.  Exceptions  were 
frequently   met   with,   but   careful   observation  of  these 


Fig.  I o I . — ' '  Pancreatic  "  reaction-de- 
posit from  a  normal  urine  treated  by  the 
A-method  (X   192). 


248       The  Pancreas:  Its  Surgery  and  Pathology 

points  was  often  found  to  be  of  considerable  assistance 
in  diagnosing  the  condition.  The  most  striking  excep- 
tions were  encountered  in  cases  of  pancreatic  cancer,  for 
while  there  was,  in  some  cases,  a  much  more  abundant 
deposit  than  usual,  and  this  was  found  to  consist  of 
slender  readily  soluble  crystals,  in  others  a  deposit  of 
the  more  characteristic,  coarse  crystals  was  only  secured 
after  repeated  trials  with  different  periods  of  boiling. 

The  results  obtained  by  this  method,  although  sug- 
gestive of  some  difference  in  the  composition  of  the  urine 
from  pancreatic  and  non-pancreatic  cases,  and  possibly 
also  in  different  types  of  pancreatic  disease,  were  not 
sufficiently  distinctive  to  be  entirely  relied  upon  for  pur- 
poses of  diagnosis,  and  further  investigation  was  obviously 
necessary.  After  considerable  experiment  we  found  that 
the  formation  of  the  crystals  in  the  A-reaction  was  pre- 
vented, or  interfered  with,  in  inflammation  of  the  pancreas 
by  preliminary  treatment  of  the  urine  with  perchloride 
of  mercury,  while  such  treatment  did  not  affect  the  ap- 
pearance of  the  crystals  in  cancer  of  the  pancreas  and 
other  conditions  that  gave  rise  to  a  positive  reaction. 
This  differential  test,  which  we  described  as  the  "  B- 
reaction,"  was  carried  out  as  follows: 

Ten  cubic  centimetres  of  the  filtered  urine  were  tho- 
roughly mixed  with  10  c.c.  of  a  saturated  solution  of 
perchloride  of  mercury  in  distilled  water.  After  standing 
for  a  few  minutes  the  mixture  was  filtered  through  a  well 
moistened  filter-paper,  and  to  10  c.c.  of  the  filtrate  i  c.c. 
of  strong  hydrochloric  acid  was  added.  It  was  then 
boiled  on  the  sand-bath  for  five  to  ten  minutes,  and  di- 
luted with  5  c.c.  of  the  mixed  urine  and  mercuric  chloride 
solution  with  10  c.c.  of  distilled  water.  After  being 
cooled  in  running  water  the  excess  of  acid  was  neutralised 
with  lead  carbonate  and  the  succeeding  stages  of  the 
operation  carried  out  as  in  the  "A-reaction." 

The  indications  given  by  a  comparison  of  the  results 


Chemical  Pathology 


249 


yielded  by  these  two  reactions  proved,  in  our  hands, 
of  very  considerable  assistance  in  diagnosis,  and  enable4 
us  to  arrive  at  a  correct  opinion  in  several  cases  where  the 
clinical  signs  and  symptoms  were  doubtful  or  misleading. 
The  results  obtained  in  the  examination  of  five  hundred 
specimens  of  urine,  two  hundred  and  ninety-seven  of  which 
were  from  patients  in  whom  there  was  evidence  of  pan- 
creatic disease  at  operation  or  post-mortem,  and  two  hun- 
dred and  eighty-three  from  normal  individuals  or  patients 
suffering  from  diseases  in  which  there  was  no  reason  to 
think  that  the  pancreas  was  involved,  are  shown  in  the 
subjoined  table: 

RESULTS  OF  THE   "A  AND  B-PANCREATIC"  REACTION  IN 
FIVE  HUNDRED  CONSECUTIVE  EXAMINATIONS. 


Group. 

Diagnosis. 

No. 

A  Deposit 
Greater 
ThanB. 

A  AND  B 

Deposit 
Equal  IN 
Amount. 

A  and  B  Both 
Negative. 

I 

Acute  pancreatitis 

4 

4 

II 

Chronic  pancreatitis: 
(a)  With   obstruction 

of  common  duct .... 
(6)  No  obstruction  of 

common  duct 

68 
116 

49 
98 

19 
15 

3 

Ill 

Cancer  of  the  pancreas    . 

29 

8 

21 

IV 

No  pancreatitis: 

(a)  Gall-stones  in  gall- 
bladder or  common 
duct 

56 

117 

7 
9 

31 
132 

18 

(6)  Miscellaneous 

36 

V 

Normal 

50 

II 

39 

From  this  it  will  be  seen  that,  as  a  rule,  the  deposit 
yielded  by  the  A-reaction  was  greater  than  that  obtained 
by  the  B-method  in  those  cases  where  there  was  evidence 
of  pancreatitis,  but  that  in  those  instances  where  the  pan- 
creas was  not  inflamed  there  was  no  reaction,  or  the 
amount  of  precipitate  was  approximately  the  same  in  the 


250       The  Pancreas:  Its  Surgery  and  Pathology 

two  preparations.  In  the  majority  of  the  cancer  cases 
examined  the  result  was  similar  to  that  obtained  in  non- 
pancreatic disease,  but  in  about  25  per  cent,  there  was  an 
appreciable  difference  in  the  amount  of  deposit  yielded 
by  the  A-  and  B-reactions. 

Like  most  comparative  tests,  to  which  accurate  meas- 
urements cannot  be  applied,  this  method  suffered  from 
the  great  disadvantage  of  being  dependent,  to  a  certain 
extent,  on  the  experience  of  the  observer  for  its  inter- 
pretation. Further,  unless  considerable  care  was  exer- 
cised in  the  details  of  the  experiment  errors  in  technique 
were  liable  to  occur  and  confuse  the  issue,  as  the  published 
accounts  of  some  who  have  attempted  to  use  these  reac- 
tions for  diagnostic  purposes  have  shown.  To  overcome 
these  difficulties  and,  as  far  as  possible,  eliminate  the  per- 
sonal element,  we  have  introduced  an  "improved "  or  "C- 
reaction,"  in  which  the  presence  or  absence  of  pancreati- 
tis is  indicated  by  the  examination  of  a  single  preparation. 
The  manipulation  is  slightly  more  complicated  and  still 
requires  a  reasonable  amount  of  skill  and  care,  particu- 
larly in  the  details  of  the  experiment,  but  the  result  is  an 
absolute  one,  and  is  therefore  independent  of  the  personal 
bias  of  the  investigator. 

Examination  of  the  phenylhydrazin  precipitate  de- 
rived from  the  urine  in  cases  of  pancreatic  inflam- 
mation, after  treatment  with  hydrochloric  acid,  showed 
that  it  consisted  of  two  parts,  one  a  phenylhydrazin 
compound  of  glycuronic  acid  and  the  other  the  osa- 
zone  of  a  sugar.  Although  there  is  reason  to  believe 
that  the  excretion  of  glycuronic  acid  is  increased  in 
pancreatitis,  an  augmentation  of  the  output  occurs  in 
so  many  pathological  conditions  that  no  helpful  diagnos- 
tic method  could  be  based  upon  this,  in  the  present  state 
of  our  knowledge.  On  turning  to  the  precipitate  ob- 
tained from  the  urine  after  treatment  with  mercuric 
chloride  we  found  that  it  consisted  entirely,  or  almost 


Chemical  Pathology  251 

entirely,  of  a  glycuronic  acid  compound  of  phenylhydra- 
zin,  so  that  the  difference  noticed  between  the  A-  and  B- 
reactions  in  characteristic  cases  of  pancreatic  inflamma- 
tion appeared  to  be  dependent  upon  the  presence  of  the 
sugar.  By  collecting  large  quantities  of  urine  from 
well-marked  cases  of  pancreatitis,  we  are  able  to  investi- 
gate the  characters  of  this,  and  found  that  it  gave  the 
reactions  of  a  pentose.  As  we  have  already  said,  we 
have  been  unable  to  discover  any  evidence  of  the  presence 
of  a  pentose  in  the  untreated  urine  from  any  of  our  cases, 
so  that  it  was  probable  that  the  pentose  giving  rise  to 
the  characteristic  "pancreatic"  reaction  was  formed  by 
hydrolysis  from  some  antecedent  substance  in  the  urine 
during  the  process  of  heating  it  with  the  dilute  acid. 

We  are  not  as  yet  in  a  position  to  make  any  definite  state- 
ments with  regard  to  the  nature  of  the  mother-substance 
from  which  the  sugar  is  derived,  but  our  earlier  experi- 
ments proved  that  it  was  not  the  so-called  animal  gum 
of  the  urine,  and  the  fact  that  a  positive  reaction  has  not, 
so  far,  been  obtained  by  the  "improved  method"  with 
the  urine  from  any  but  pancreatic  cases  suggests  that  it  is 
probably  a  body  resulting  from  changes  in  the  pancreas, 
and  possibly  derived  directly  from  that  organ.  The 
relatively  large  proportion  of  pentose-yielding  material 
in  the  pancreas,  as  shown  by  Neuberg,  who  gives  the 
following  as  the  results  of  his  analyses  of  various  organs : 

1 


Pancreas 

Liver 0.56% 

Thymus 0.56% 

Submaxillary  gland.  •  .  0.53% 

Thyroid 0.50% 

Kidney 0.49% 

Spleen 0.46% 

Brain 0.22% 

Muscle 0.11% 


As   pentose   in   the   dry 
'        substance 


points  to  the  pancreas  as  the  most  likely  source.  It  can- 
not be  denied,  however,  that  the  disintegration  of  other 
tissues  may  also,   at  times,  influence  the  urine  in  this 


252       The  Pancreas:  Its  Surgery  and  Pathology 

respect,  and  it  has  also  to  be  remembered  that  the  inges- 
tion of  large  amounts  of  penton-containing  food  materials 
may  also  cause  small  quantities  of  pentose  to  be  excreted 
in  the  urine;  therefore,  while  we  maintain  that  a  positive 
reaction  by  the  ' '  improved  method' '  of  performing  the 
so-called  "pancreatic  reaction"  is  strongly  suggestive 
of  inflammatory  disease  of  the  pancreas,  we  are  not  pre- 
pared to  contend  that  it  is  pathognomonic  of  pancreatitis. 

The  ' '  improved  method, ' '  or  "  C-reaction, ' '  is  based  upon 
the  different  behaviour  of  glycuronic  acid  and  the  sugars, 
in  acid  solutions,  to  tribasic  lead  acetate,  the  former 
being  precipitated  and  the  latter  remaining  in  solution. 
If  therefore  the  acid  filtrate,  left  after  the  urine  has  been 
boiled  with  hydrochloric  acid  and  the  excess  of  acid 
neutralised  with  lead  carbonate,  is  treated  with  tribasic 
lead  acetate,  the  glycuronic  acid  set  free  in  the  process 
will  be  thrown  out,  while  any  sugar  remaining  in  the 
solution  can  be  detected  by  the  phenylhydrazin  test, 
after  the  precipitate  has  been  filtered  off  and  the  excess  of 
lead  removed  by  appropriate  methods. 

In  performing  the  reaction  a  specimen  of  the  twenty-four 
hours  urine,  or  of  the  mixed  evening  and  morning  secre- 
tions, is  filtered  several  times  through  the  same  filter-paper. 
If  it  is  found  to  be  free  from  sugar  and  albumin,  and  is  acid 
in  reaction,  2  c.c.  of  strong  hydrochloric  acid  (sp.  gr.  1.16) 
are  mixed  with  40  c.c.  of  the  clear  filtrate,  and  the  mix- 
ture gently  boiled  on  a  sand-bath  in  a  small  flask,  fitted 
with  a  funnel  condenser  (Fig.  97).  After  ten  minutes' 
boiling  the  flask  is  well  cooled  in  a  stream  of  water,  and 
the  contents  made  up  to  40  c.c.  with  cold  distilled  water. 
The  excess  of  acid  is  then  neutralised  by  slowly  adding  8 
grams  of  lead  carbonate.  After  standing  for  a  few  min- 
utes to  allow  of  the  completion  of  the  reaction,  the  flask 
is  again  cooled  in  running  water,  and  the  contents  filtered 
through  a  well-moistened,  close-grained  filter-paper  until 
a  perfectly  clear  filtrate  is  obtained.     The  acid  filtrate  is 


Chemical  Pathology  253 

then  well  shaken  with  8  grams  of  powdered  tribasic  lead 
acetate,  and  the  resulting  precipitate  removed  by  filtra- 
tion, as  clear  a  filtrate  as  possible  being  secured  by  repeat- 
ing the  filtrate  several  times  if  necessary.  Since  the  large 
amount  of  lead  now  in  solution  would  interfere  with  the 
subsequent  steps  of  the  experiment,  it  is  removed,  either 
by  a  stream  of  sulphuretted  hydrogen,  or,  what  we  have 
found  to  be  equally  satisfactory  and  less  disagreeable, 
by  precipitating  the  lead  as  a  sulphate.  For  this  purpose 
the  filtrate  is  well  shaken  with  4  grams  of  powdered  sodium 
sulphate,  the  mixture  heated  to  the  boiling-point,  then 
cooled  to  as  low  a  temperature  as  possible  in  a  stream  of 
cold  water,  and  the  white  precipitate  removed  by  careful 
filtration.  Ten  cubic  centimetres  of  the  perfectly  clear, 
transparent  filtrate  are  taken  and  made  up  to  17  c.c.  with 
distilled  water ;  it  is  then  added  to  0.8  gram  of  phenylhy- 
drazin  hydrochl orate,  2  grams  of  sodium  acetate,  and  i 
c.c.  of  50  per  cent,  acetic  acid,  contained  in  a  small  flask 
fitted  with  a  funnel  condenser.  The  mixture  is  boiled  on 
a  sand-bath  for  ten  minutes  and  filtered  hot  through  a 
small  filter-paper,  moistened  with  hot  water,  into  a  test- 
tube  provided  with  a  15  c.c.  -mark.  Should  the  filtrate 
fall  short  of  15  c.c,  it  is  made  up  to  that  amount  with  hot 
distilled  water,  the  added  water  being  well  mixed  with 
the  fluid  by  stirring  with  a  glass  rod,  but  in  our  own 
work  we  find  that  any  addition  is  rarely  necessary,  as, 
with  a  little  practice,  it  is  possible  to  so  regulate  the  boil- 
ing that  the  final  result  almost  always  comes  out  at  between 
15  and  16  c.c. 

In  well-marked  cases  of  pancreatic  inflammation  a 
light  yellow,  flocculent  precipitate  should  appear  in  a 
few  hours,  but  in  less  characteristic  cases  it  may  be 
necessary  to  leave  the  preparation  over-night  before 
a  deposit  occurs.  Under  the  microscope  the  precip- 
itate is  seen  to  consist  of  long,  light -yellow,  flexible, 
hair-like    crystals    arranged   in    delicate    sheaves,    which 


254       The  Pancreas:  Its  Surgery  and  Pathology 

when  irrigated  with  33  per  cent,  sulphuric  acid  melt  away 
and  disappear  in  ten  to  fifteen  seconds  after  the  acid  first 
touches  them.  The  preparation  must  always  be  examined 
microscopically,  as  a  small  deposit  may  be  easily  over- 
looked with  the  naked  eye,  and  it  is  also  difficult  to  deter- 
mine the  exact  nature  of  a  slight  precipitate  by  macro- 
scopical  investigation  alone. 

To  exclude  traces  of  sugar,  undetected  by  the  prelimi- 


Fig.  102. — Improved,  or  C-,  "pancreatic"  reaction-crystals  from  a 
case  of  chronic  pancreatitis  with  gall-stones  in  the  common  bile-duct 
(X  200). 


nary  reduction  tests,  a  control  experiment  is  carried  out 
by  treating  40  c.c.  of  the  filtered  urine  in  the  same  way  as 
that  in  the  test  just  described,  except  that  it  is  not  boiled 
with  hydrochloric  acid.  Any  albumin  that  may  be  present 
in  the  urine  is  removed,  previous  to  commencing  the  test, 
by  faintly  acidulating,  boiling,  filtering  off  the  albuminous 
precipitate,  cooling,  and  making  the  specimen  up  to  its  orig- 
inal bulk  with  distilled  water.     The  urine  employed  for 


Chemical  Pathology 


•:)D 


the  experiment  should  be  fresh,  and  not  have  undergone 
fermentative  changes.  If  alkaline  in  reaction,  it  should 
be  made  distinctly  acid  with  hydrochloric  acid  before  the 
test  is  commenced.  Any  dextrose  that  may  be  present 
can  be  removed  by  fermentation  after  the  urine  has  been 
boiled  with  the  acid  and  the  excess  neutralised.  The 
administration  of  calcium  chloride,  as  advised  by  one  of 
us  in  all  cases  of  pancreatic  disease  previous  to  operation, 
has  been  found  to  interfere  with  the  success  of  the  reaction. 
In  the  following  table  the  results  obtained  by  this 
method  in  two  hundred  consecutive  examinations,  in 
which  it  has  been  possible  to  confirm  the  diagnosis  post- 
mortem or  at  operation,  are  given,  and,  for  the  sake  of 
comparison,  the  findings  in  fifty  specimens  from  presuma- 
bly healthy  persons  are  also  included : 


RESULT  OF  THE  "IMPROVED"  OR  " C-PANCREATIC  REAC- 
TION" IN  TWO  HUNDRED  AND  FIFTY  CONSECUTIVE 
EXAMINATIONS. 


Group. 

Diagnosis. 

No. 

Positive. 

Negative. 

I 

Acute  pancreatitis 

2 

2 

II 

Chronic  pancreatitis : 

(a)  With   obstruction   of  the 
common  duct: 

(i)  By  gall-stones 

(2)   By  growth 

(6)   No  obstruction  of  common 

19 
2 

19 
2 

duct : 

(i)  No  gall-stones  found .. . 

32 

32 

(2)   Gall-stones      in      gall- 

bladder  

12 

12 

Ill 

Cancer  of  the  pancreas 

16 

4 

1 2 

IV 

No  pancreatitis: 

(a)   Gall-stones     in     common 

duct 

10 

10 

(b)   Gall-stones    in    gall-blad- 

der   

II 
96 

4 

1 1 

{c)  Miscellaneous 

92 

V 

Normal 

5° 

50 

256       The  Pancreas:  Its  Surgery  and  Pathology 

It  will  be  seen  that  a  positive  reaction  was  obtained  in 
seventy-five,  and  that  in  one  hundred  and  twenty-five  no 
crystalline  deposit  was  observed.  Two  of  the  former  were 
cases  of  acute  pancreatitis.  In  thirty-three  there  was 
chronic  pancreatitis,  associated  with  gall-stones  in  the 
common  duct  in  nineteen,  with  growth  of  the  common 
duct  invading  the  pancreas  in  two,  and  with  stones  in 
the  gall-bladder  in  twelve.  In  twelve,  although  the 
pancreas  was  stated  to  be  distinctly  larger  and  harder 
than  normal  when  examined  at  operation,  no  biliary 
calculi  were  found,  but  in  one  of  these  cases  gall-stones 
were  found  in  a  specimen  of  feeces  examined  at  the  same 
time  as  the  urine,  and  in  another  several  had  been  found 
in  the  stools  shortly  before  the  examination  was  made. 
There  was  an  ulcer  of  the  duodenum  in  six,  a  gastric  ulcer 
adherent  to  the  pancreas  in  one,  in  three  there  were  nu- 
merous adhesions  about  the  head  of  the  gland.  Of  the 
sixteen  cases  of  cancer  of  the  pancreas,  twelve  gave  no 
reaction,  but  in  four  a  more  or  less  marked  deposit  of 
crystals  was  obtained.  In  addition  to  the  twelve  cases 
of  cancer  just  mentioned,  no  reaction  was  obtained  in  ten 
specimens  from  cases  where  gall-stones  were  found  in  the 
common  duct  at  the  time  of  operation  and  the  pancreas 
was  said  to  be  normal ;  in  eleven  where  biliary  calculi  were 
present  in  the  gall-bladder,  but  no  evidence  of  pancrea- 
titis was  found  either  pathologically  or  clinically ;  and  in 
ninety-two  samples  from  cases  of  miscellaneous  diseases, 
including  cancer  of  the  stomach,  colon,  rectum,  or  liver, 
gastric  ulcer,  duodenal  ulcer,  gastritis,  colitis,  appen- 
dicitis, tuberculosis  of  the  intestine,  intestinal  obstruc- 
tion, cirrhosis  of  the  liver,  hepatic  abscess,  nephritis, 
floating  kidney,  tuberculosis  of  the  kidney,  cystitis, 
mumps,  and  Addison's  disease.  In  four  cases  of  cancer 
of  the  stomach  or  duodenum  a  positive  reaction  was  ob- 
tained, but  in  these  the  growth  was  adherent  to  the  pan- 
creas.    One,  in  which  the  growth  was  situated  in  the 


Chemical  Pathology  257 

first  part  of  the  duodenum,  gave  no  reaction  when  first 
examined,  and  on  abdominal  section  it  was  then  found 
that  the  pancreas  was  free;  but  a  month  later,  when  a 
positive  reaction  was  obtained,  a  second  exploratory 
operation  showed  that  the  pancreas  had  become  involved 
in  the  growth.  No  reaction  was  obtained  with  any  of 
the  fifty  specimens  from  apparently  healthy  individuals. 
On  looking  through  the  table  it  is  interesting  to  note  that 
nineteen  out  of  the  twenty-nine  cases  (or  65  per  cent.) 
in  which  gall-stones  were  found  in  the  common  duct  at 
the  time  of  operation  gave  a  positive  reaction,  whereas 
ten  (or  35  per  cent.)  gave  no  reaction,  which  corresponds 
fairly  closely  with  the  62  per  cent,  and  38  per  cent, 
given  by  Helly  as  the  proportion  of  cases  in  which  the 
common  bile-duct  is  embraced  by,  and  free  from,  the 
pancreas  respectively. 

The  urines  from  twenty- two  cases,  which  previous  to 
operation  had  given  a  well-marked  reaction,  were  re- 
examined one  to  two  weeks  after  cholecystenterostomy 
had  been  performed  for  the  relief  of  pancreatitis,  but  no 
reaction  could  be  obtained,  and  in  four  cases  where  an 
opportunity  presented  itself  of  making  a  further  investi- 
gation at  a  subsequent  date,  one  three  months,  another 
six  months,  a  third  seven  months,  and  the  fourth  nine 
months  after  operation,  there  was  still  no  reaction. 

It  has  been  possible  to  test  the  findings  of  the  "pan- 
creatic" reaction  in  twenty-four  cases  by  histological 
examination  of  the  pancreas.  In  one  a  small  piece  of  the 
gland  was  removed  at  operation  and  showed  evidence  of 
interstitial  pancreatitis,  which  confirmed  the  diagnosis 
based  upon  the  urine  examined.  The  remaining  twenty- 
three  were  examined  post-mortem.  Three  were  cases  of 
cancer  of  the  pancreas.  In  one,  where  the  whole  organ 
was  invaded  by  the  growth,  the  results  of  the  examina- 
tion of  the  urine  had  suggested  during  life  that  there  was 
a  considerable  chronic  inflammation;  in  the  other  two 
17 


258       The  Pancreas:  Its  Surgery  and  Pathology 


pig_  lo^, — Microphotographs  of  the  pancreas  from  six  cases  the 
urine  of  which  had  given  during  life  a  well-marked  "pancreatic"  reac- 
tion (X  ca  40). 


Chemical  Pathology  259 

the  disease  chiefly  affected  the  head  of  the  gland  and  a 
correct  diagnosis  had  been  arrived  at.  Eleven  had  been 
diagnosed  from  the  urinary  reaction  as  chronic  pancrea- 
titis. In  ten  of  these  a  more  or  less  marked  overgrowth 
of  the  interstitial  connective  tissue  was  found  microscop- 
ically (Fig.  103).  It  is  noteworthy  that  in  four  of  them, 
although  the  organ  had  been  said  at  operation  to  be  larger 
and  harder  than  usual,  no  pathological  change  could  be 
detected  by  the  naked  eye  after  death.  In  one  case  no 
interstitial  overgrowth  could  be  discovered  either  macro- 
scopically  or  microscopically,  but  the  blood-vessels  were 
much  dilated  and  there  were  small  patches  of  round- 
celled  infiltration  in  the  neighbourhood  of  the  ducts, 
pointing  to  an  early  inflammatory  change.  No  reaction 
suggestive  of  a  pancreatic  lesion  had  been  obtained  in 
the  remaining  nine  cases  during  life,  and  post-mortem 
the  pancreas  appeared  to  be  normal,  both  to  the  naked 
eye  and  on  microscopical  examination. 

It  has  been  contended  by  Ham  and  Cleland  that  the 
crystals  obtained  from  the  urine  by  the  A-  and  B -reac- 
tions are  crystals  of  a  lead  salt,  formed  by  the  action  of 
phenylhydrazin  and  sodium  acetate  upon  the  lead  car- 
bonate used  in  neutralising  the  hydrochloric  acid  em- 
ployed in  the  test,  and  that  therefore  the  results  obtained 
by  these  methods  are  absolutely  unreliable.  The  un- 
soundness of  this  argument  is  at  once  apparent  when  it  is 
remembered  that  sulphuric  acid,  neutralised  with  barium 
carbonate,  or  nitric  acid  neutralised  with  urea,  give 
similar  results,  and  that  hydrochloric  acid  was  only 
selected  for  routine  work  because  it  gave  cleaner  prepara- 
tions and  its  action  was  more  easily  controlled.  Lead 
carbonate  was  selected  as  the  neutralising  agent,  since 
the  caustic  alkalies  were  found  to  interfere  with  the 
reaction,  and  lead  was  the  most  insoluble  chloride  that 
could  be  formed. 

There  are  possibly  some,  however,  who,  in  consequence 


26o       The  Pancreas:  Its  Surgery  and  Pathology 

of  this  and  similar  criticism,  are  unconsciously  biased 
against  the  reaction,  and  on  this  account  it  may  not  be 
out  of  place  if  we  here  summarise  the  arguments  brought 
forward  by  these  and  other  writers,  and  briefly  consider 
the  experimental  data  on  which  they  were  based. 

The  conclusion  reached  by  Ham  and  Cleland  was  arrived 
at  on  the  following  grounds:  (i)  They  stated  that  they 
were  able  to  obtain  crystals  from  all  urines,  provided 
that  the  solution  was  sufficiently  concentrated  by  boiling ; 
(2)  rosettes  of  pale  crystals  were  also  obtained  when  the 
reaction  was  performed  with  distilled  water;  (3)  if  the 
urine  or  distilled  water,  after  being  boiled  with  hydro- 
chloric acid,  and  neutralised  with  lead  carbonate,  was 
treated  with  ammonium  sulphide,  filtered,  and  boiled, 
the  reaction  with  phenylhydrazin  was  prevented;  (4) 
lead  acetate  solution  treated  with  sodium  acetate  and 
phenylhydrazin  hydrochlorate  gave  fine  needle-like  crys- 
tals in  rosettes  and  sheaves. 

There  is  no  doubt  that  a  soluble  lead  salt  does  form 
needle-like  crystals  when  boiled  with  sodium  acetate 
and  phenylhydrazin  hydrochlorate,  but  these  crystals 
never  appear  in  a  properly  performed  "pancreatic" 
reaction,  and,  should  they  do  so,  can  be  easily  distin- 
guished from  the  true  osazone  crystals  by  the  naked- 
eye  characters  and  their  appearance  under  the  micro- 
scope. They  are  very  much  larger  (Fig.  104),  colourless 
instead  of  yellow,  and  form  solid  masses  at  the  bottom 
of  the  test-tube  or  appear  as  tufts  adherent  to  its 
walls.  In  a  carefully  performed  reaction  the  quantity 
of  lead  that  passes  into  the  filtrate  is  small,  and  does  not 
in  any  way  affect  the  results  of  the  test,  but  if,  from 
faults  of  manipulation  or  errors  in  technique,  a  large 
amount  is  present,  it  is  not  unlikely  to  give  rise  to  difficul- 
ties in  inexperienced  hands,  especially  when  the  preparation 
has  been  unduly  concentrated  by  excessive  or  furious 
boiling.     It  is  to  this  cause  that  the  positive  reactions 


Chemical  Pathology 


261 


obtained  by  Ham  and  Cleland  with  all  urines  and  with 
distilled  water  were  no  doubt  due.  The  removal  of  any 
lead  in  solution,  moreover,  does  not  interfere  with  the 
success  of  the  reaction,  as  these  writers  state;  indeed, 
this  is  intentionally  done  in  the  "improved  reaction," 
as  there  the  large  amount  of  lead  acetate  employed  would 


Fig.  104. — Microphotograph  of  the  "lead-salt  crystals"  formed  as 
the  result  of  faulty  technique  in  carrying  out  the  "pancreatic"  reaction 
by  the  original  A-method  (X  200). 


introduce  a  serious  difficulty,  unless  it  were  removed 
before  performing  the  phenylhydrazin  test.  Ammonium 
sulphide  cannot,  however,  be  used  for  the  purpose,  as 
the  ammonia  set  free  destroys  any  sugar  that  may  be 
present  when  the  fluid  is  subsequently  heated,  but  Ham 
and  Cleland  do  not  appear  to  have  considered  that,  when 
using  ammonium  sulphide  in  the  manner  they  describe, 
they  were  possibly  performing  a  modification  of  Moore's 
test  for  sugar.     Finally,  the  fact  that  the  purified  crystals 


262       The  Pancreas:  Its  Surgery  and  Pathology 

from  the  urine  in  cases  of  pancreatic  disease  have  a  defi- 
nite melting-point,  are  free  from  any  trace  of  lead,  and 
correspond  in  their  other  characters  with  osazone  crys- 
tals, conclusively  proves  that,  when  the  reaction  is  care- 
fully and  properly  performed,  they  are  not  "lead  salt 
crystals." 

In  a  paper  on  "the  use  of  phenylhydrazin  in  the  clinical 
examination  of  urine"  W.  H.  Willcox  gives  an  account  of 
some  experiments  which  were,  more  or  less,  based  upon 
the  reactions  described  in  our  original  communications, 
and  he  there  states  that  "the  production  of  characteristic 
yellow  crystals  in  the  urine  after  hydrolysis  with  hydro- 
chloric acid  can  in  no  sense  be  used  as  a  specific  test  for  any 
pathological  conditions,  since  such  crystals  are  constantly 
obtained  from  normal  urines."  The  experimental  por- 
tions of  this  paper  cover  much  of  the  ground  traversed  by 
us  previous  to  the  elaboration  of  the  "pancreatic"  reac- 
tion, but  we  cannot  confirm  all  the  results  or  agree  with 
the  deductions  drawn  from  them.  We  are  quite  willing 
to  admit  that  "the  production  of  characteristic  crystals 
in  the  urine  after  hydrolysis  cannot  be  used  as  a  specific 
test  for  any  pathological  condition,"  including  pancrea- 
titis, if  the  method  employed  is  that  of  the  author  of 
that  paper,  but  we  do  maintain  that,  if  the  methods  we 
have  described  are  carefully  and  conscientiously  carried 
out,  and  the  results  considered  in  conjunction  with  the 
clinical  symptoms,  and  the  indications  given  by  other 
methods  of  pathological  research,  the  presence  of  pan- 
creatitis can  be  determined  with  very  much  greater  cer- 
tainty than  by  the  clinical  evidence  alone.  Our  results 
with  normal  urines  do  not  correspond  with  those  obtained 
by  Willcox,  as  the  tables  on  pages  249  and  255  show. 
We  do  not  think  that  any  difficulty  of  diagnosis  was  likely 
to  arise  even  with  a  normal  urine  when  the  original  A- 
and  B -reactions  were  employed,  but  the  "improved 
method"  has  now  got  rid  of  any  slight  difficulty  that  there 


Chemical  Pathology  263 

might  possibly  be  and  has  simplified  the  diagnosis  of 
pancreatitis  from  non-pancreatic  diseases. 

J.  H.  Schroeder  and  P.  S.  Haldane  have  published  some 
criticisms  of  our  original  methods  under  the  mistaken 
idea  that  we  claimed  to  have  proved  the  presence  of 
glycerine  in  the  urine  of  patients  suffering  from  diseases 
of  the  pancreas.  The  glycerine  theory  was  but  a  working 
hypothesis  on  which  we  commenced  our  investigations, 
and,  as  we  have  explained,  had  to  be  abandoned  as  the 
research  proceeded.  They  also  assume  that  the  crystals 
obtained  in  acute  and  chronic  pancreatitis  and  in  cancer 
of  the  pancreas  by  the  A-reaction  are  identical,  and  point 
out  that  they  are  therefore  unlikely  to  have  different  shapes 
and  solubilities.  The  assumption  is  without  foundation, 
for  the  difference  in  appearance  and  in  rate  of  solution 
in  sulphuric  acid  is  due  to  the  differences  of  chemical 
composition. 

Fat-splitting  Ferment  {Opie). — Since  the  fat  necrosis 
associated  with  acute  pancreatitis  is  due  to  the  fat- 
splitting  ferment  of  the  pancreatic  juice,  it  occurred 
to  Opie  that  this  ferment,  which  is  free  in  the  tissues, 
might  be  excreted  by  the  kidneys.  In  one  case,  in 
which  he  tested  the  truth  of  this  assumption,  he  found 
evidence  that  tended  to  show  that  such  an  excretion 
did  occur.  The  specimen  of  urine  examined  was  taken, 
after  death,  from  the  body  of  a  man  who  died  of  heemor- 
rhagic  pancreatitis.  It  was  neutralised  with  potassium 
hydrate  and  divided  into  two  parts.  To  one  a  few  drops 
of  ethyl  butyrate  and  a  little  neutral  litmus  were  added. 
The  other  was  treated  in  the  same  way,  after  any  fer- 
ment present  had  been  destroyed  by  boihng.  Both 
specimens  were  incubated  at  37°  C.  for  twenty-four  hours. 
At  the  end  of  that  time  the  unboiled  specimen  had  ac- 
quired a  well-marked  acid  reaction,  while  the  control 
specimen  showed  little,  if  any,  change.  We  have  not 
had  the  opportunity  of  carrying  out  a  similar  test  in  a  case 


264       The  Pancreas:  Its  Surgery  and  Pathology 

of  acute  inflammation  of  the  pancreas,  but  in  two  cases 
of  subacute  pancreatitis,  and  several  of  chronic  pancrea- 
titis, in  which  we  have  employed  it  no  difference  could  be 
observed  between  the  two  preparations. 

Lipuria  has  been  described  by  some  writers  as  occurring 
in  disease  of  the  pancreas.  Clark  and  Bowditch  have 
reported  cases  of  cancer  of  the  gland  in  which  fat  globules 
were  present  in  the  urine.  Tulpius  and  Elliotson  also 
record  similar  cases,  but  without  any  other  confirmatory 
evidence  of  pancreatic  disease  than  the  presence  of  fat 
in  the  stools.  In  a  case  of  acute  pancreatitis,  operated 
on  seventy- two  hours  after  the  onset,  Cooke  found  fat  in 
the  urine  on  one  occasion.  We  have  met  with  lipuria 
only  once  in  our  series  of  cases,  and  that  was  in  a  case  of 
chronic  pancreatitis  in  a  woman,  aged  forty-four,  the 
cause  being  apparently  an  extension  from  duodenal 
catarrh.  It  was  associated  with  liporrhoea,  azotorrhoea, 
and  bulky  stools,  and  with  a  well-marked  pancreatic 
reaction  in  the  urine.  The  abdomen  was  opened  and  a 
swelling  of  the  pancreas  was  discovered  with  a  number 
of  adhesions  surrounding  it,  but  no  gall-stones  were 
found.  Drainage  of  the  bile-ducts  by  a  simple  cholecys- 
totomy  completely  cured  the  pancreatic  condition,  and 
when  the  urine  was  examined  a  year  later  there  was  an 
entire  absence  of  the  pancreatic  reaction. 

Fat  is  met  with  in  the  urine  in  so  many  different  con- 
ditions, and  is  so  rarely  found  in  pancreatic  disease,  that 
its  association  with  lesions  of  the  pancreas  is  possibly  acci- 
dental. It  is  to  be  remembered,  however,  that  lipuria 
occurs  in  diabetes  mellitus,  and  that  in  this  disease  a  large 
amount  of  fat  is  also  occasionally  encountered  in  the  blood. 

Detection  of  Pancreatic  Enzymes. — It  is  sometimes  neces- 
sary to  determine  whether  a  pathological  fluid,  obtained 
from  a  cyst  or  fistula,  has  originated  in  connection  with  the 
pancreas.  The  general  physical  and  chemical  characters  of 
the  fluid  may  afford  some  indication  of  its  probable  source, 


Chemical  Pathology  265 

but  the  most  reliable  proof  is  obtained  by  an  investiga- 
tion of  its  behaviour  to  proteids,  fats,  and  carbohydrates. 
When  the  fluid  is  found  to  contain  ferments  capable  of 
readily  digesting  all  three  forms  of  food  material  there  can 
be  little  doubt  as  to  its  origin.  The  presence  of  a  diastatic 
ferment  alone  is  of  little  value  in  diagnosis,  since  diastase 
may  be  met  with  in  other  fluids  of  the  body.  The  detec- 
tion of  a  proteolytic  ferment,  capable  of  digesting  albu- 
min in  an  alkaline  medium,  is  much  more  important, 
for  no  other  ferment  than  trypsin  can  dissolve  albumin 
in  the  presence  of  an  alkali.  It  is  frequently  found, 
however,  that  the  contents  of  cysts,  undoubtedly  of  pan- 
creatic origin,  have  little  or  no  proteolytic  power.  This  is 
stated  to  be  particularly  the  case  with  old  encapsuled 
cysts  of  long  standing.  It  has  to  be  remembered,  how- 
ever, that  the  normal  pancreatic  juice  possesses  but  feeble 
powers  of  digesting  proteid  until  it  has  been  activated  by 
the  enterokinase  of  the  intestine,  so  that  the  absence  of 
this  property  in  the  contents  of  pancreatic  cysts  is  not 
surprising.  The  observation  of  Delezenne  that  the  addi- 
tion of  a  small  quantity  of  a  soluble  calcium  salt  activates 
the  pancreatic  secretion  as  powerfully,  but  more  slowly, 
than  enterokinase  suggests  a  way  of  overcoming  the  diffi- 
culty when  examining  the  contents  of  a  cyst  for  diagnos- 
tic purposes.  The  power  of  splitting  neutral  fats  into 
glycerine  and  fatty  acids  is  the  most  characteristic  prop- 
erty of  pancreatic  juice,  and  unless  a  pathological  fluid 
possesses  this  property  it  cannot  be  stated,  with  certainty, 
that  it  has  originated  in  connection  with  the  pancreas. 

The  method  of  testing  for  the  proteolytic  ferment  devel- 
oped by  Boas  is  that  which  has  been  usually  employed. 
The  fluid  to  be  examined  is  added  to  milk,  placed  for 
some  time  in  an  incubator,  and,  after  the  casein  has 
been  precipitated,  is  examined  by  the  biuret  reaction.  A 
positive  result  of  the  test  indicates  that  the  fluid  can 
digest  albumin  in  the  presence  of  an  alkaline  reaction. 


266       The  Pancreas:  Its  Surgery  and  Pathology 

Pawlow,  in  his  investigations  of  the  digestive  juices, 
employed  Mett's  tubes,  and  these  have  the  advantage 
that  they  afford  a  means  by  which  the  digestive  power 
of  the  fluid  can  be  expressed  numerically  for  purposes  of 
comparison.  Egg-albumen  is  employed  in  this  method 
and  the  tubes  containing  it  are  prepared  as  follows: 
The  egg-albumen  is  filtered  through  gauze  into  a  small 
beaker,  or  wide  test-tube,  and  short  glass  tubes,  having 
a  lumen  of  about  2  mm.,  are  slowly  dropped  into  it.  Air- 
bubbles  are  allowed  to  escape,  aided  by  gentle  tapping, 
and  the  vessel  containing  the  tubes  is  then  placed  in  a 
bath  of  boiling  water  for  five  or  ten  minutes.  The  flame 
is  removed  and  the  glass  allowed  to  cool  for  several  hours. 
The  test-tube  or  beaker  is  then  broken,  and  the  small 
tubes  filled  with,  and  embedded  in,  the  coagulated  albu- 
men are  cut  out  and  preserved  in  glycerine.  One  of  the 
tubes  is  used  for  each  test.  It  is  first  washed  with  water, 
then  placed  in  a  test-tube  containing  the  fluid  to  be  tested, 
which,  if  necessary,  has  previously  been  made  faintly 
alkaline.  After  being  incubated  for  from  three  to  ten 
hours,  the  small  tube  is  examined  and  the  presence  of  a 
proteolytic  ferment  is  shown  by  a  portion  of  the  column 
of  coagulated  albumen  having  been  dissolved.  To  de- 
termine the  digestive  power  of  the  fluid,  the  length  of  the 
tube,  and  of  the  undigested  remains  of  the  proteid  col- 
umn, are  measured  off  on  a  millimetre  scale  with  a  low 
power  of  the  microscope ;  the  difference  gives  the  length 
of  the  digested  cylinder  in  millimetres  and  fractions  of  a 
millimetre.  The  quantity  of  proteolytic  ferment  in  the 
fluid  is  proportional  to  the  square  of  the  column  of  albu- 
men digested  in  a  definite  time. 

The  fat-splitttng  ferment  may  be  tested  for  by  the  method 
of  Castle  and  Loevenhart,  in  which  purified  ethyl  buty- 
rate  and  neutral  litmus  are  added  to  the  fluid  to  be  ex- 
amined (see  "Opie's  test"  for  fat-splitting  ferments  in 
the  urine,  page  263).     A  neutral  fat,  obtained  by  tho- 


Chemical  Pathology  267 

roughly  shaking  olive  oil  with  sodium  carbonate  solution 
and  ether,  pipetting  off  the  ethereal  layer,  filtering  it  if 
necessary,  and  then  recovering  the  fat  from  the  ether  by 
allowing  the  latter  to  evaporate,  may  be  used  instead  of 
ethyl  butyrate.  A  numerical  expression  of  the  fat-splitting 
power  of  the  fluid  may  be  obtained  by  titrating  the  acidity 
of  the  emulsion,  after  it  has  been  incubated  for  a  definite 
period  with  periodical  shaking,  with  baryta  solution. 

The  diastatic  ferment  can  be  recognized  by  incubating 
the  fluid  with  boiled  starch  paste,  and  then  testing  for 
sugar  with  Fehling's  solution.  The  activity  of  the  fer- 
ment may  be  determined  by  titrating  the  sugar,  formed 
in  a  given  time  from  a  definite  amount  of  starch  paste, 
with  Fehling's  solution,  but  the  more  rapid  method  advo- 
cated by  Pawlow  gives  results  that  are  sufficiently  reliable. 
This  is  a  modification  of  Mett's  method  for  proteolytic 
ferments.  Thin  glass  tubes  filled  w4th  coloured  starch 
paste  are  incubated  with  the  fluid  to  be  tested  for  a  defi- 
nite time, — half  an  hour  is  usually  sufficient, — and  then 
examined  with  a  lower  power  of  the  microscope.  The 
activity  of  the  amylolytic  ferment  is  found  to  follow  the 
same  law  as  the  proteolytic  and  vary  directly  as  the  square 
of  the  column  digested  in  a  given  time. 

In  all  investigations  on  the  digestive  power  of  fluids 
it  is  advisable  to  conduct  a  control  experiment  with  a 
portion  of  the  material  that  has  been  boiled  to  destroy 
any  ferments  that  may  be  present,  so  that  in  making  the 
final  deductions  it  may  be  used  as  a  standard  of  compari- 
son. The  action  of  bacteria  should  also  be  excluded  by 
adding  to  both  the  test  fluid  and  to  the  control  a  mild 
antiseptic,  such  as  thymol. 

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1904. 
Ziehl:   Deutsch.  med.  Wochenschr.,  1883,  Nr.  37. 


CHAPTER  XI 
DIABETES 

The  dependence  of  diabetes  upon  disease  of  the  pan- 
creas was  first  suggested  by  Bouchardat  in  1875,  and, 
although  two  years  later  Lancereaux  emphasised  the 
importance  of  the  connection,  and  sought  to  distinguish 
a  special  type  of  the  disease  which  he  believed  was  always 
associated  with  profound  alterations  in  the  structure  of 
the  panceas,  it  was  not  until  the  classical  experiments  of 
von  Mering  and  Minkowski  were  published  in  1889  that  the 
pancreatic  theory  of  diabetes  was  placed  upon  a  firmly 
established  footing. 

The  failure  of  experimental  attempts  to  produce  dia- 
betes through  damming  back  the  pancreatic  juice  by 
ligature  of  the  ducts,  or  by  conveying  the  secretion  out- 
side the  body  by  a  fistula,  had  led  such  an  authority  as 
Cohnheim  to  regard  all  pancreatic  changes  met  with  in 
diabetics  as  secondary,  or  accidental,  complications.  It 
was  recognised,  however,  that  the  pancreas  might  exert  an 
influence  on  carbohydrate  metabolism  through  some  other 
channel  than  its  external  secretion,  but  complete  extirpa- 
tion of  the  organ  in  dogs  was  so  speedily  followed  by  the 
death  of  the  animals  from  shock,  hemorrhage,  injury  to 
the  duodenum,  or  peritonitis,  that  no  opportunity  was 
afforded  of  observing  the  remote  effects  of  the  operation. 

Martinotti,  in  1888,  was  the  first  to  successfully  over- 
come these  difficulties  and  to  point  out  that  the  failure 
of  previous  experimenters  might  be  avoided  by  rigid 
antisepsis,  careful  ligature  of  all  bleeding  vessels,  and 
preservation  of  the  vascular  supply  of  the  duodenum. 
It  was  not  until  the  following  year,  however,  that  the 

269 


270       The  Pancreas:  Its  Surgery  and  Pathology 

physiological  relation  of  the  pancreas  to  carbohydrate 
metabolism  was  conclusively  proved  by  the  publication 
of  von  Mering  and  Minkowski's  work. 

These  and  other  observers  have  shown  that  total  extir- 
pation of  the  pancreas  in  dogs  gives  rise  to  a  condition  com- 
parable in  every  respect  to  diabetes  as  seen  in  man.  Usually 
within  twenty-four  hours  of  the  operation  the  urine  con- 
tains sugar,  which  gradually  increases  in  amount  until  it 
reaches  a  maximum  of  8  to  10  per  cent,  about  the  third  day. 
On  a  diet  of  bread  and  meat  a  dog  of  8  kilos  is  then  found 
to  pass  from  70  to  80  grams  of  sugar  in  the  twenty-four 
hours,  and  even  after  seven  days'  starvation  glycosuria 
is  still  present.  The  amount  of  sugar  in  the  urine  in  the 
latter  case  bears  a  constant  ratio  to  the  nitrogen  of  about 
2.8  :  I,  suggesting  that  the  total  quantity  of  sugar  formed 
from  albumin  within  the  body  is  being  excreted  unutil- 
ised by  the  tissues.  Although  dextrose  given  with  the 
food  is  passed  in  its  entirety  into  the  urine,  Isevulose  is 
made  use  of  to  a  fairly  large  extent,  in  contrast  to  what 
is  found  to  be  the  case  in  diseases  of  the  liver  (Strauss). 
There  is  a  marked  increase  in  the  quantity  of  urine  passed, 
a  dog  of  7  kilos  voiding  from  1000  to  1200  c.c.  in  the 
twenty-four  hours.  Although  an  animal  from  which  the 
pancreas  has  been  removed  eats  and  drinks  voraciously, 
it  rapidly  wastes  and  loses  strength,  so  that  death  takes 
place  from  inanition  in  about  four  weeks,  even  when 
lung  disease,  or  trouble  arising  from  the  invariable  disin- 
clination of  the  operation  wound  to  heal,  does  not  bring 
about  a  fatal  issue  at  an  earlier  date.  When  the  animal 
is  too  weak  to  move  about,  the  excretion  of  sugar  begins 
to  diminish,  although  food  is  being  taken,  and  a  few  days 
before  death  it  may  altogether  disappear,  especially 
when  there  is  suppurative  peritonitis.  Coincidentally 
with  the  fall  in  the  excretion  of  sugar,  acetone,  diacetic 
acid,  and  /3-oxybutyric  acid  make  their  appearance  in 
the  urine.     When  the  animal  is  killed  a  few  days  after 


Diabetes 


271 


the  operation,  the  glycogen  normally  present  in  the  liver 
and  other  organs  is  found  to  be  absent,  or  only  present 
in  small  amounts,  unless  it  has  been  fed  with  laevulose 
in  the  interval,  when  a  high  percentage  may  be  met  with. 
Examination  of  the  blood  shows  that  it  contains  a  jjro- 
portion  of  sugar  much  in  excess  of  the  normal  o.  i  per  cent., 
sometimes  as  much  as  0.4  per  cent,  being  found,  and  that 
when  the  ureters  are  tied  or  the  kidneys  are  removed  the 
proportion  is  still  further  increased,  thus  pointing  to  the 
accumulation  of  sugar  in  the  blood  as  the  immediate 
cause  of  the  glycosuria. 

The  effects  of  removing  the  pancreas  have  been  most 
thoroughly  and  completely  investigated  in  dogs,  but 
analogous  results  have  also  been  obtained  with  many 
other  members  of  the  vetebrate  series,  including  cats  and 
pigs  (Minkowski  and  Harley),  carnivorous  birds  (Wein- 
traud,  Kausel,  and  Langendorff ) ,  frogs  and  turtles  (Alde- 
hoff  and  Markuse),  eels  (Capparelli).  The  proportion  of 
sugar  in  the  blood  has  been  shown,  by  Kausel,  to  be  in- 
creased in  herbivorous  birds  by  removing  the  pancreas, 
but  glycosuria  was  found  to  only  occasionally  occur, 
probably  because  the  kidneys  of  these  animals  are  not 
readily  pervious  to  sugar.  Experiments  performed  upon 
rabbits  have  usually  been  unsuccessful,  because  of  the 
great  technical  difficulties  encountered  in  totally  extirpat- 
ing the  gland,  but  Hedon,  and  later  Sauerbeck,  have 
succeeded  in  producing  atrophy  and  transient  glyco- 
suria by  injecting  oil  into  the  duct  of  Wirsung,  the  gly- 
cosuria appearing  at  the  earliest  on  the  twentieth  day, 
and  being  at  its  height  from  the  thirtieth  to  the  thirty- 
eighth  day  after  the  injection. 

Partial  extirpation  of  the  pancreas  may  or  may  not 
give  rise  to  diabetes,  according  to  the  amount  left  behind 
and  its  condition.  If  about  a  fourth  or  fifth  of  the  gland 
is  left,  glycosuria  only  occurs  if  carbohydrates  are  present 
in   the   food  (" alimentary  glycosuria").     A   larger   por- 


272       The  Pancreas:  Its  Surgery  and  Pathology 

tion  usually  prevents  the  condition.  Less  generally  gives 
rise  to  frank  diabetes.  Even  when  sugar  does  not  appear 
in  the  urine  after  partial  extirpation  it  will  do  so  if  the 
remnant  is  subsequently  removed,  and  may  gradually 
develop  as  the  fragment  atrophies.  Sandmeyer  found 
that  the  first  trace  of  sugar  appeared  in  the  urine  of  a  dog, 
part  of  whose  pancreas  he  had  removed,  seven  weeks 
after  the  operation,  and  it  was  not  until  after  the  lapse 
of  thirteen  and  a  half  months  that  permanent  diabetes 
developed.  Death  occurred  eight  months  later.  At 
the  post-mortem  a  remnant  weighing  0.36  gram,  and 
showing  no  trace  of  gland  structure,  was  found  adherent 
to  the  posterior  wall  of  the  stomach,  while  attached  to 
the  lowest  part  of  the  duodenum  was  a  piece  of  slightly 
changed  gland-tissue  the  size  of  a  pea. 

The  first  explanation  of  the  results  of  these  experiments 
that  suggests  itself  is  that  the  removal  of  the  pancreas 
leads  to  impaired  digestion  from  absence  of  the  pancreatic 
juice,  and  that  this  is  in  some  way  responsible  for  the 
onset  of  glycosuria.  But  the  fact  that  diabetic  symptoms 
do  not  supervene  unless  almost  the  entire  gland  has  been 
removed  is  against  such  a  theory;  moreover,  if  the  se- 
cretion of  the  gland  is  diverted,  and  intestinal  digestion 
thus  prevented,  diabetes  does  not  follow,  although  marked 
wasting  may  occur.  Ligature  of  the  pancreatic  duct 
likewise  fails  to  give  rise  to  glycosuria,  as  a  rule. 

Disease  of  the  solar  plexus  has  been  regarded  by  some  as 
a  cause  of  the  diabetes,  and,  as  the  plexus  is  almost  unavoid- 
ably injured  in  the  removal  of  the  pancreas,  this  might 
possibly  be  the  explanation  of  the  symptoms  caused  by  the 
depancreatisation  of  animals.  It  was  shown  by  Minkowski, 
however,  that  if  the  descending  portion  of  the  gland  is 
transplanted  into  the  subcutaneous  tissue  of  the  abdom- 
inal wall,  and  allowed  to  become  engrafted  there,  the 
intra-abdominal  portion  can  be  removed,  after  the  graft 
has  been  severed  from  all  its  nervous  connections,  without 


Diabetes  273 

producing  diabetes,  but  that  if  the  graft  is  subsequently 
removed — or  atrophies — diabetes  develops. 

The  cause  of  the  glycosuria,  and  of  the  accumulation 
of  sugar  in  the  blood,  appears  therefore  to  be  dependent 
upon  some  influence  which  the  pancreas  exerts  by  way 
of  the  blood  or  lymph  stream.  There  are  two  possible 
means  by  which  this  can  be  effected:  first,  it  may  be  that 
the  cells  of  the  pancreas  normally  destroy,  or  modify, 
some  toxic  substance,  produced  in  other  parts  of  the 
body,  which  interferes  with  the  utilisation  of  sugar  by 
the  tissues;  or,  secondly,  that  the  pancreas  produces  an 
internal  secretion  which  is  necessary  for  the  splitting  up 
and  use  of  sugar  by  the  other  cells  of  the  organism. 

The  first,  or  auto-intoxication,  theory  is  that  which  was 
originally  favoured  by  Minkowski,  but  it  was  later  aban- 
doned by  him  in  favour  of  the  second  hypothesis.  Bosan- 
quet,in  his  Goulstonian  lectures,  favours  the  view  that  dia- 
betes, is  due  to  an  increased  internal  dissociation  of  tissue 
(possibly  fat)  into  sugar,  caused  by  a  toxic  substance  that  is 
produced  in  the  course  of  normal  metabolism,  and  which 
is  normally  neutralised  by  the  pancreas.  He  points  out 
that  poisonous  doses  of  phloridzin,  diuretin,  and  uranium 
nitrate  give  rise  to  glycosuria,  and  that  suprarenal  extract 
and  other  reducing  substances,  when  applied  directly  to 
the  pancreas,  produce  a  similar  effect.  That  it  is  not 
necessary  for  the  bulk  of  the  blood  to  come  into  actual 
contact  with  the  pancreatic  cells  to  prevent  hypergly- 
csemia  and  glycosuria  is  suggested  by  the  restraining  effect 
of  even  a  small  proportion  of  the  pancreatic  tissue,  and  by 
the  results  of  grafting  a  portion  of  the  gland  into  the 
abdominal  wall,  for  under  such  conditions  only  a  small 
fraction  can  be  directly  influenced  by  the  gland  cells. 
It  is  possible,  however,  that  when  only  a  small  part  of  the 
pancreas  is  left  in  an  experimental  partial  extirpation  of 
the  gland,  a  sufficient  amount  of  an  internal  secretion  may 
pass  into  the  bloodstream  to  neutralise  any  toxic  substance 


274       The  Pancreas:  Its  Surgery  and  Pathology 

that  may  be  present  there.  Tuckett  has  suggested  that 
the  pancreas  normally  forms  such  an  internal  secretion, 
which  enters  the  circulation  by  way  of  the  thoracic  duct, 
and  there  neutralises  a  toxine  absorbed  by  the  lymphatics 
from  the  intestine  during  digestion.  In  support  of  his 
hypothesis  he  states  that  if  the  thoracic  lymph  from  a 
fasting  dog  is  injected  into  the  portal  circulation  of  a  cat, 
no  hyperglycasmia  or  glycosuria  results;  but  that  if  the 
lymph  from  a  dog  during  digestion  is  similarly  injected,  a 
hyperglycsemia,  varying  from  0.3  to  0.9  per  cent.,  and  a 
glycosuria,  varying  from  i.o  to  9.0  per  cent.,  are  pro- 
duced. Confirmation  of  his  results  is,  however,  as  yet 
lacking.  Minkowski  has  shown  that  if  the  efferent  vessels 
from  a  pancreatic  graft  are  ligatured,  so  as  to  ensure  that 
all  the  returning  blood  is  passed  into  the  general  circula- 
tion, diabetes  does  not  develop,  thus  demonstrating  that 
the  transmission  of  the  efferent  blood  into  the  portal 
circulation  is  not  necessary  to  prevent  the  onset  of  glyco- 
suria. As  the  result  of  experiments  upon  dogs  Lorand 
has  recently  stated  that  there  is  a  relation  between  the 
islands  of  Langerhans  and  the  thyroid,  the  former  secret- 
ing a  substance  which  neutralises  a  poison  produced  by  the 
latter,  and  that  diabetes  may  arise  either  from  increased 
functional  activity  of  the  thyroid  or  from  failure  of  the 
cell  islets  to  perform  their  function. 

The  theory  that  the  blood  normally  contains  a  sugar- 
splitting  ferment,  which  is  absent  in  diabetes,  was  warmly 
advocated  by  Lepine,  who  stated  that  the  blood  of  dia- 
betics has  a  diminished  capacity  for  transforming  sugar. 
■Crofton,  who  supported  Lepine's  observations,  claimed  to 
have  isolated  the  ferment  by  which  glycolysis  is  brought 
about,  and  to  have  identified  it  with  trypsin.  Other 
observers  have  found,  however,  that  when  precautions  are 
taken  to  prevent  contamination,  normal  blood  possesses 
no  glycolytic  power,  and  have  regarded  the  positive 
results  as  being  due  to  the  action  of  micro-organisms. 


Diabetes  275 

Indeed,  Lepine  himself  subsequently  gave  up  the  idea 
that  glycolysis  occurs  in  the  blood,  and  referred  it  to  the 
tissue  cells. 

Blumenthal  and  others  have  asserted  that  the  cells 
from  the  pancreas,  liver,  spleen,  muscle,  etc.,  possess 
a  strong  glycolytic  power;  which  is  much  increased 
if  pancreatic  extract  be  mixed  with  the  cell  juice  from 
other  organs.  Giacco  found  that  this  power  varied  in 
different  organs,  being  great  in  the  heart  and  little  in 
the  pancreas  itself.  He  also  stated  that  it  was  not  a  vital 
phenomenon,  for  it  persisted  after  the  tissues  had  been 
boiled.  According  to  Umber,  however,  when  careful 
precautions  are  taken  against  contamination  with  micro- 
organisms, the  tissues  outside  the  body  exhibit  only  very 
slight  glycolytic  powers.  The  same  observer  also  found 
that  the  sugar-splitting  power  of  the  blood  was  not  greater 
in  the  pancreatic  vein  than  in  the  general  arterial  or 
venous  systems,  as  it  would  have  been  if  the  pancreas 
secreted  a  sugar-destroying  substance. 

An  explanation  of  the  phenomena  of  glycolysis  on  the 
lines  of  Ehrlich's  "side-chain"  theory  has  been  advanced 
by  Cohnheim,  for  he  found  that  expressed  muscle  juice  is 
inactive  to  sugar  until  it  has  been  mixed  with  expressed 
tissue  juice  from  the  pancreas,  or  with  an  ether  precipitate 
from  it.  From  this  he  argues  that  the  muscle  produces  a 
ferment  which  is  itself  incapable  of  decomposing  sugar,  but 
which,  when  acted  on  by  an  "  activator  substance"  derived 
from  the  pancreas,  gains  that  power,  in  much  the  same  way 
as  a  complement  and  amboceptor  are  necessary  for  hsemo- 
lysis  and  analogous  processes.  The  presence  of  blood  in 
the  muscle  was  found  to  cause  glycolysis  without  the  addi- 
tion of  pancreatic  extract,  indicating  that  the  activator 
substance  derived  from  the  pancreas  was  present  in  the 
blood.  This  substance  Cohnheim  states  is  soluble  in 
water  and  alcohol,  but  is  insoluble  in  ether,  and,  since  it  is 
not  destroyed  by  boiling,  he  concludes  that  it  is  not  a 


276       The  Pancreas:  Its  Surgery  and  Pathology 

ferment,  but  analogous  to  adrenalin,  iodothyrin,  secretin, 
and  other  products  of  internal  secretion.  Cohnheim's 
methods  and  conclusions  have  been  criticised  by  Claus 
and  Embden,  who  were  unable  to  confirm  his  results,  but 
the  main  fact  that  the  pancreas  gives  rise  to  an  activator 
substance  for  a  glycolytic  enzyme  produced  by  other 
tissues  of  the  body  appears  to  have  since  been  firmly  es- 
tablished. Experiments  have  been  conducted  by  Pavy 
which  point  to  a  "co-ferment-like,  or  activator  sub- 
stance," being  yielded  by  the  pancreas,  which  aids  in  the 
synthetic  process  concerned  in  the  linking-on  of  sugar  in 
the  construction  of  proteid,  and  the  absence  of  which 
would  lead  to  failure  of  carbohydrate  assimilation  and 
the  condition  met  with  in  diabetes. 

There  is  little  or  no  doubt  that  the  nervous  system  plays 
a  part  in  the  production  of  some  forms  of  diabetes,  and, 
although  the  experiments  already  detailed  show  that 
injury  of  the  nerves  in  the  neighbourhood  of  the  pancreas 
is  not  responsible  for  the  symptoms  caused  by  extirpa- 
tion of  the  gland,  it  is  possible  that  indirectly  the  nutri- 
tion of  the  nerve  centres  may  be  influenced  in  such  a  way 
as  to  produce  metabolic  changes  in  the  pancreas  and 
other  tissues  of  the  body.  There  is,  however,  no  experi- 
mental work  to  support  such  a  view,  and  it  is  now  gener- 
ally admitted  that  the  most  satisfactory  explanation  of 
pancreatic  diabetes  is  that  which  supposes  that  the  disease 
is  due  to  the  absence  of  some  ferment,  or  co-ferment-like 
body,  which  normally  reaches  the  blood  from  the  gland. 

Injury  or  rough  handling  of  the  pancreas,  painting  it 
with  piperidine,  nicotine,  coniine,  pyridine,  adrenalin,  etc., 
are  said  to  give  rise  to  transitory  glycosuria.  This  subject 
has  been  recently  re-investigated  by  Underbill,  who  found 
that  "  insults"  of  the  gland,  by  freezing  with  ethyl  chloride 
or  rough  handling,  caused  neither  hyperglycasmia  nor 
glycosuria,  but  that  the  application  of  the  drugs  referred 
to   gave   rise   to   both.     Further   investigation   showed, 


Diabetes  277 

however,  that  suppression  of  the  respiratory  process,  to 
the  point  of  dyspnoea,  caused  an  increase  of  sugar  in  the 
blood  which  could  be  prevented  by  the  administration 
of  oxygen,  and  that  a  similar  use  of  oxygen  also  prevented 
the  hyperglycasmia  generally  following  the  application  of 
piperidine  and  all  the  other  substances  mentioned,  except 
adrenalin,  so  that  they  appeared  to  act  through  the  blood 
upon  the  respiratory  centre.  The  action  of  adrenalin 
appeared,  however,  to  be  directly  upon  the  pancreas,  and 
was  unique  in  this  respect. 

The  view  has  been  held  by  some  authors  that  diabetes 
is  an  infectious  disorder,  and  since,  as  we  have  already 
seen,  changes  may  be  brought  about  in  the  structure  of 
the  pancreas  by  the  action  of  micro-organisms  and  their 
toxines,  it  is  not  impossible  that,  at  least  in  some  instances, 
a  microbic  infection  may  give  rise  to  the  disease.  Ham- 
marschlag  and  KaufEmann  have,  indeed,  succeeded  in 
producing  glycosuria  by  feeding  animals  upon  bacteria 
obtained  from  the  intestines  of  diabetics,  and  by  injecting 
them  intravenously,  but  evidence  that  it  was  a  true  dia- 
betes is  lacking,  and  there  is  no  proof  that  the  infection 
was  specific. 

The  first  recorded  case  in  which  disease  of  the  pan- 
creas was  noticed  to  be  associated  with  diabetes  was 
described  by  Cowley  in  1 788.  In  this  the  gland  was  found 
to  be  atrophied  and  to  contain  calculi  in  its  ducts.  Cho- 
part  described  a  similar  case  in  1821,  and  Bright,  in  1833, 
gave  an  account  of  a  diabetic,  nineteen  years  of  age,  with 
jaundice  and  fatty  stools,  the  head  of  whose  pancreas  was 
found  at  the  post-mortem  to  be  converted  into  a  hard, 
nodtdar  tumour,  firmly  adherent  to  the  duodenum.  Sub- 
sequently other  cases  were  published  by  Elliotson,  Fre- 
richs,  Hartsen,  Fles,  von  Recklinghausen,  Munk,  Silver, 
and  Bouchardat,  but  the  first  to  definitely  propound  the 
theory  of  pancreatic  diabetes  was  Lancereaux,  in  1877. 
He    claimed    that    diabetes,    accompanied    by  wasting 


278       The  Pancreas:  Its  Surgery  and  Pathology 

("diabete  maigre"),  was  due  to  disease  of  the  pancreas, 
while  that  in  which  there  was  no  marked  loss  of  flesh 
("diabete  gras")  arose  from  some  other  cause.  The 
pancreatic  type  of  the  disease,  he  believed,  was  also 
characterised  by  the  bnisqueness  of  its  onset,  the  gravity 
of  the  symptoms,  and  the  rapid  progress  of  the  disease. 
Subsequent  observation  has  not  confirmed  the  clinical 
distinctions  thus  drawn  by  Lancereaux;  in  fact,  many 
cases  of  glycosuria,  of  undoubted  pancreatic  origin,  are  of 
insidious  onset,  progress  but  slowly,  and  show  no  marked 
loss  of  flesh.  We  have  had  the  opportunity  of  observing 
several  cases  in  which  glycosuria  has  developed  after 
operations  for  gall-stones,  or  disease  of  the  pancreas, 
and  have  been  much  struck  by  the  slow  progress  of  the 
disease  and  generally  good  condition  of  the  patient,  even 
after  the  lapse  of  several  years.  One  patient  who  was 
operated  on  twelve  years  ago  for  gall-stones  was  found  to 
have  glycosuria  eight  and  a  half  years  after  the  operation, 
and  still  passes  a  considerable  amount  of  sugar  in  the 
urine,  but  enjoys  good  general  health.  In  another  and 
similar  case  the  glycosuria  has  persisted  for  six  years,  and 
in  a  third  case  of  cholelithiasis  associated  with  glycosuria, 
in  which  we  have  repeatedly  had  the  opportunity  of  exam- 
ining the  urine,  the  patient  was  said  to  be  alive  and  well, 
except  for  some  local  irritation  due  to  the  sugar,  five 
years  after  the  operation  and  the  discovery  of  the  glyco- 
suria. 

It  it  now  generally  acknowledged  that  the  character  of 
the  symptoms  affords  no  clue  as  to  the  pancreatic  or 
non-pancreatic  origin  of  the  disease,  and  that  attempts 
to  make  a  clinical  distinction  are  usually  unsuccessful, 
except  in  those  instances  where  a  history  of  past  disease 
of  the  pancreas  affords  an  indication.  It  is  impossible, 
therefore,  to  judge  from  bedside  experience  how  far 
pancreatic  disease  is  responsible  for  diabetes  in  man.  On 
turning  to  post-mortem  records  for  information  on  this 


Diabetes  279 

point,  we  are  at  once  confronted  by  the  divergent  ex- 
perience of  different  observers.  Windle  reported  that 
in  one  hundred  and  thirty-nine  cases  of  diabetes  the  pan- 
creas was  diseased  in  seventy-four  (53  per  cent.).  Seegen 
analysed  the  records  of  ninety-two  cases  and  found  a  pan- 
creatic lesion  in  seventeen  (19  per  cent.).  P>erichs  in 
forty-four  cases  found  disease  of  the  pancreas  in  sixteen 
(36  per  cent.).  Out  of  fifty-four  cases  of  diabetes,  ex- 
amined in  the  Berlin  Pathological  Institute,  Hansemann 
reports  that  there  was  a  lesion  of  the  pancreas  in  forty 
(17  per  cent.).  Bloch,  quoted  by  Oser,  collected  twenty- 
two  cases,  from  the  records  of  the  Vienna  General  Hos- 
pital, in  twelve  (55  per  cent.)  of  which  the  pancreas  had 
been  recognised  as  abnormal.  Williamson  examined 
twenty-three  cases  and  in  fifteen  (65  per  cent.)  found 
evidence  of  pancreatic  disease.  Opie  investigated  the 
pancreas  in  nineteen  cases  of  diabetes  and  detected  some 
abnormality  of  the  gland  in  fifteen  (79  per  cent).  Bosan- 
quet  records  nineteen  cases,  in  seventeen  (90  per  cent.) 
of  which  there  was  disease  of  the  pancreas. 

These  different  results  are  no  doubt  to  a  great  extent  de- 
pendent upon  a  divergence  of  opinion  as  to  what  may  be 
regarded  as  normal  and  what  as  pathological  when  examin- 
ing the  pancreas  in  the  post-mortem  room,  and  also  to  the 
use  of  the  microscope  by  modern  observers  as  an  aid  to 
diagnosis  in  some  instances.  Opie,  who  made  a  histological 
examination  of  the  gland  in  the  nineteen  cases  he  investi- 
gated, found  evidence  of  disease  in  all  but  four  (21  per 
cent.),  whereas  Seegen,  out  of  his  ninety- two  cases,  states 
that  the  organ  was  normal  in  seventy-five  (81  per  cent.) ; 
in  four  of  Opie's  cases,  however,  no  gross  abnormality 
could  be  detected,  and  it  was  not  until  they  were  sub- 
mitted to  microscopical  investigation  that  a  lesion  was 
discovered.  The  statistics  of  the  older  observers,  not 
based  upon  careful  macroscopical  and  microscopical 
examination,  are  therefore  probably  of  little  value,  and, 


28o       The  Pancreas:  Its  Surgery  and  Pathology 

as  the  number  of  instances  in  which  such  investigations 
have  been  performed  is  as  yet  too  small  to  allow  of  any 
reliable  inference  being  drawn,  no  definite  answer  can  be 
given  to  the  question  as  to  what  proportion  of  cases  of 
diabetes  are  due  to  disease  of  the  pancreas?  Opie  con- 
siders that  in  considerably  more  than  half  the  disease 
results  from  a  destructive  lesion  of  the  gland,  while 
Bosanquet  thinks  that  "it  is  becoming  increasingly 
probable  that  the  pancreas  is  diseased  in  all  cases  of 
diabetes  mellitus." 

On  attempting  to  determine  from  published  reports  the 
relative  frequency  in  diabetes  of  the  various  diseases  to 
which  the  pancreas  is  liable,  the  difficulty  of  reconciling 
the  results  obtained  by  different  investigators  is  again 
encountered.  According  to  the  older  observers,  the  most 
common  lesion  is  atrophy  of  the  gland.  Windle  found  it 
in  over  59  per  cent,  of  the  cases  he  investigated  and  Fre- 
richs  in  75  per  cent.  The  statistics,  quoted  by  Hanse- 
mann,  from  the  Berlin  hospitals  in  the  space  of  ten  years, 
show  forty  cases  of  diabetes  with  disease  of  the  pancreas, 
in  thirty-six  (90  per  cent.)  of  which  there  was  simple 
atrophy,  and  in  three  (8  per  cent.)  atrophy  and  sclerosis. 
The  more  recent  observations  of  Williamson  and  Opie, 
however,  give  much  lower  figures,  the  former  finding 
simple  atrophy  in  four  out  of  eleven  cases  (27  percent.), 
and  the  latter  in  four  out  of  fifteen  (26  per  cent.).  Some 
explanation  of  this  difference  is  afforded  by  the  more 
careful  and  exact  methods  of  investigation  employed  in 
recent  years,  and  there  is  no  doubt  that  in  the  past  too 
great  a  reliance  upon  the  naked-eye  characters  caused 
many  cases  in  which  the  size  of  the  pancreas  appeared 
diminished  to  be  classified  as  simple  atrophy,  which  were, 
in  reality,  examples  of  the  atrophic  changes  resulting 
from  chronic  inflammation  of  the  gland.  The  form  of 
atrophy  which  Hansemann  considered  was  always  asso- 
ciated with  diabetes  appears  to  belong  to  this  class,  and 


Diabetes  281 

although  there  is  no  means  of  determining  whether  the 
atrophy  of  the  pancreatic  cells  leads  to  the  increase  of 
fibrous  tissue,  or  the  fibrosis  results  from  inflammatory 
changes  in  the  gland,  and  then,  by  its  contraction,  pro- 
duces alterations  in  the  glandular  acini,  it  is  now  gener- 
ally considered  that  the  fibrosis  is  the  principal  lesion, 
and  the  cell  atrophy  a  minor  phenomenon.  Simple 
atrophy,  therefore,  although  it  may  be  the  only  lesion 
found  in  some  cases  of  diabetes,  would  not  appear  to  play 
such  an  important  part  in  the  production  of  the  disease  as 
was  at  one  time  supposed,  and  there  is  no  evidence  to  show 
that  the  pancreas  is  liable  to  a  particular  form  of  atrophy 
which  invariably  gives  rise  to  diabetes. 

In  a  few  cases  of  diabetes  fatty  degeneration  of  the 
pancreas  has  been  found,  after  death,  as  the  only  discover- 
able lesion.  Bosanquet  met  with  a  recognisable  degree 
of  fatty  change  in  ten  out  of  one  hundred  cases,  which,  in 
three,  was  combined  with  some  fibrosis.  Williamson  in 
his  series  met  with  one  case  of  lipomatosis,  in  which  there 
was  atrophy  and  fatty  degeneration,  and  one  where, 
besides  atrophy  and  fatty  degeneration,  there  were  evi- 
dences of  inflammatory  changes. 

The  earliest  recorded  case  in  which  disease  of  the  pan- 
creas was  recognised  as  being  associated  with  diabetes 
was,  as  we  have  seen,  one  of  pancreatic  calculi.  But  as 
Hansemann  was  only  able  to  find  fourteen  instances  in 
seventy-two  cases  (19  per  cent.)  collected  from  medical 
literature,  and  Oser  quotes  but  twenty-four  examples  in 
one  hundred  and  eighty-eight  cases  of  diabetes  (14  per 
cent.),  the  association  is  not  a  very  common  one,  particu- 
larly as  the  lesion  is  so  obvious  that  it  would  not  be  readily 
overlooked.  The  mere  presence  of  calculi  cannot  be 
regarded  as  directly  responsible  for  the  diabetes,  for 
blocking  of  the  ducts,  by  ligature  or  otherwise,  has  been 
proved  not  to  cause  glycosuria ;  it  is  to  the  fibrotic  changes 
accompanying  them  that  we  must  look  for  the  explanation. 


282       The  Pancreas:  Its  Surgery  and  Pathology 


That  this  is  the  true  cause  is  shown  by  the  fact  that  dia- 
betes is  only  found  in  those  cases  where  there  is  very 
marked  overgrowth  of  fibrous  tissue,  whereas  in  those 
instances  where  the  concretions  are  not  associated  with 
advanced  interstitial  changes  glycosuria  does  not  occur. 

In  a  similar  way,  although  cysts  of  the  pancreas  have 
been  found  in  from  5  per  cent.  (Oser)  to  7  per  cent.  (Dieck- 
hoff)  of  diabetics  showing  a  pancreatic  lesion,  there  are 
many  cases  of  cysts  in  which  glycosuria  does  not  occur. 

In  some  instances 
sugar  may  appear 
in  the  urine  some 
time  after  a  cyst 
has  been  recog- 
nised and  surgically 
treated,  owing 
probably  to  the 
advance  of  the 
chronic  inflamma- 
tory changes  to 
which  the  forma- 
tion of  the  cyst  was 
originally  due. 

We  have  had  the 
opportunity  of  in- 
vestigating a  case 
of  this  description  through  the  kindness  of  Dr.  Chur- 
ton,  under  whose  care  it  came  at  the  General  In- 
firmary, Leeds.  The  patient  was  operated  on  by  one 
of  us  in  June,  1896,  for  a  cyst  of  the  pancreas.  The 
urine  was  then,  free  from  sugar  and  showed  no  other 
abnormality,  save  that  it  gave  a  well-marked  "pancre- 
atic" reaction.  In  February,  1905,  we  heard  that  the 
patient  had  been  admitted  to  the  Infirmary  suffering 
from  diabetes,  and,  by  the  courtesy  of  the  house  physician, 
we  were  able  to  obtain  a  twenty-four  hour  sample  of  the 


Fig.  105. — Fibrosis  of  the  pancreas,  from 
a  case  of  diabetes  associated  with  the  pres- 
ence of  pancreatic  calculi  (X   32). 


Diabetes 


283 


urine  and  a  specimen  of  the  faeces.  The  former  measured 
62  ounces,  was  strongly  acid  in  reaction,  specific  gravity 
1 .030.  There  was  no  albumin,  but  a  well-marked  reaction 
for  nucleo-proteid  was  obtained.  Acetone  was  absent, 
but  there  was  a  trace  of  diacetic  acid.  No  reaction  for 
bile-pigment,  urobilin,  or  indican  was  obtained.  The 
urine  reduced  Fehling's  solution  and  gave  a  characteristic 
reaction  with  phenylhydrazin.  Titration  with  Fehling's 
solution  showed  4.5  per  cent,  of  sugar  (80  grams  in  the 
twenty-four  hours).  No 
indication  of  the  pres- 
ence of  a  pentose  could 
be  found.  The  total  ni- 
trogen, urea,  uric  acid, 
chlorides,  phosphates, 
sulphates,  and  oxalates 
were  estimated,  and 
found  to  be  normal,  ex- 
cept that  the  oxalates 
showed  an  excess  (0.32 
gram  in  the  twenty-four 
hours).  The  "pancre- 
atic "  reaction  gave 
many  fine  crystals,  sol- 
uble in  ^^  per  cent, 
sulphuric  acid  in  ten  to 

fifteen  seconds.  The  fasces  were  of  a  light  yellow  coloiu" 
and  faintly  alkaline  in  reaction.  They  gave  a  well-marked 
reaction  for  stercobilin.  There  was  no  marked  excess  of 
unabsorbed  fat,  but  the  normal  relation  between  the 
"neutral  fats"  and  "fatty  acids"  was  disturbed,  the  for- 
mer constituting  15  per  cent,  and  the  latter  only  5  per 
cent,  of  the  dry  weight  of  the  faeces,  thus  indicating  some 
interference  with  the  digestive  functions  of  the  pancreas. 
The  association  of  cancer  of  the  pancreas  with  diabetes 
is  relatively  uncommon.     Windle  found  it  in  4  per  cent. 


Fig.  106. — Columnar-celled  car- 
cinoma of  the  pancreas  undergoing 
colloid  change,  from  a  case  of  diabetes 
(X  5°)- 


284       The  Pancreas:  Its  Surgery  and  Pathology 

of  his  cases;  Frerichs  in  6  per  cent.,  Dieckhoff  in  7  per 
cent.,  and  Williamson  once  in  his  series  of  twenty-three 
consecutive  cases.  Glycosuria  has  been  met  with  in 
only  two  of  the  forty  cases  of  primary  malignant  disease 
of  the  pancreas  in  which  we  have  had  the  opportunity  of 
examining  the  urine,  and  once  where  the  gland  was  in- 
volved in  a  secondary  growth.  The  last  is  of  particular 
interest  from  several  points  of  view,  for  it  demonstrates 
in  a  very  striking  manner  the  importance  of  the  pancreas 
in  carbohydrate  metabolism  in  the  human  subject,  and 
also  the  value  of  the  "pancreatic"  reaction  in  diagnosis. 
When  the  patient  was  first  seen,  early  in  December,  1905, 
there  was  an  abdominal  tumour  which  it  was  thought 
might  be  pancreatic,  but  a  specimen  of  urine  on  being 
submitted  for  examination  gave  no  "  pancreatic"  reaction 
and  was  free  from  sugar.  On  opening  the  abdomen  the 
tumour  was  found  to  be  due  to  a  growth  in  the  first  part 
of  the  duodenum,  and  a  gastro-enterostomy  was  therefore 
performed.  On  the  i8th  of  January  a  second  specimen 
of  urine  was  examined,  and,  although  it  was  still  free  from 
sugar,  it  was  found  to  give  a  well-marked  and  charac- 
teristic "pancreatic"  reaction,  suggesting  that  the  pan- 
creas had  now  become  involved  in  the  growth.  At  the 
request  of  the  friends,  the  abdomen  was  again  opened, 
and  it  was  seen  that  the  growth  had  invaded  the  pancreas 
and  was  beginning  to  involve  the  common  bile-duct.  As 
it  was  impossible  to  attempt  the  removal  of  the  tumour, 
a  cholecystenterostomy  was  performed.  In  May,  1906, 
the  urine  was  again  examined,  and  was  found  to  contain 
5.25  per  cent,  of  sugar;  a  month  later  this  had  increased 
to  7.0  per  cent.;  in  July  it  had  reached  7.25  per  cent. ; 
in  August,  7.5  per  cent.;  and  in  October,  9.5  per  cent. 
was  present.  In  spite  of  the  high  percentage  of  sugar  in 
the  urine  the  general  condition  of  the  patient  remained 
fairly  good  and  she  complained  of  no  other  symptoms 
than    thirst    and    a    voracious    appetite.     Considerable 


Diabetes  285 

quantities  of  acetone  and  diacetic  acid  were  present  in  the 
urine  in  May,  but  with  careful  treatment  they  gradually 
diminished  in  amount,  until  in  the  early  part  of  October 
only  traces  could  be  detected.  Toward  the  end  of  Octo- 
ber the  gall-bladder  was  found  to  be  distended  and  a  few 
days  later  jaundice  developed.  The  patient  died  deeply 
jaundiced  on  November  5,  1906. 

In  some  cases  of  malignant  disease  of  the  pancreas 
glycosuria  has  appeared  as  an  early  symptom,  which  has 
later  disappeared,  while  in  others  it  has  only  been  met 
with  towards  the  termination  of  the  disease.  The  tem- 
porary appearance  of  sugar  in  the  urine  in  these  cases  is 
possibly  dependent  upon  the  disturbance  in  the  functions 
of  the  gland,  caused  by  an  inflammatory  reaction  attendant 
upon  the  spread  of  the  growth,  which  subsequently  quiets 
down,  leaving  sufficient  unaltered  tissue  to  carry  on  the 
work  of  carbohydrate  metabolism.  In  a  case  of  this 
description  under  Macaigni,  quoted  by  Oser,  there  w^as 
transient  glycosuria  for  seven  months,  then  eleven  months' 
cachexia  without  glycosuria.  Death  took  place  twenty- 
three  months  after  the  onset  of  the  disease.  Post-mortem 
a  large,  very  hard  cancer  of  the  head  of  the  pancreas, 
replacing  one -half  of  the  gland,  was  found.  The  rest  of 
the  organ  appeared  to  be  normal.  It  has  also  to  be  borne 
in  mind  that  where  a  portion  of  the  pancreas  has  been 
destroyed  by  growth  the  condition  resembles  that  pro- 
duced in  animals  by  partial  extirpation  of  the  gland,  so 
that  if  carbohydrates  are  excluded  from  the  diet  the  ali- 
mentary glycosuria,  which  previously  existed,  may  dissap- 
pear.  In  most  recorded  cases  where  sugar  has  appeared 
in  the  urine  as  a  terminal  symptom  either  the  whole  organ 
has  been  replaced  by  a  mass  of  growth,  or  the  portions 
that  have  remained  have  undergone  sclerotic  changes, 
so  that  no  normal  pancreatic  tissue  was  left  to  carry  on 
the  functions  of  the  gland. 

The  absence  of  permanent  diabetes  in  most  cases  of 


286       The  Pancreas:  Its  Surgery  and  Pathology 

cancer  of  the  pancreas  is  due  to  the  growth  being  Hmited 
in  many  instances  to  one  portion  of  the  gland,  usually 
the  head.  In  about  29  per  cent,  of  cases,  however,  this 
explanation  will  not  hold  good,  for  in  that  proportion 
there  is  a  diffuse  growth  affecting  the  whole  organ.  It 
is  supposed  that  in  these  cases  either  the  tumour  cells 
possess  a  glycolytic  power,  or  the  new-growth  insinuates 
itself  between  the  pancreatic  cells  in  such  a  way  as  to 
obliterate  the  normal  structure  of  the  gland  without  de- 
stroying it  entirely.  That  such  a  process  of  growth  is 
possible  is  shown  by  the  presence  in  some  instances  of 
unaltered  island  of  Langerhans  in  the  midst  of  the  can- 
cerous material,  while  in  support  of  the  former  hypothesis 
Hansemann  points  out  that  in  primary  carcinoma  of  the 
suprarenals  Addison's  disease  is  rare. 

When  considering  the  general  pathology  of  the  pancreas, 
we  pointed  out  that  the  commonest  of  all  lesions  to  which 
the  organ  is  liable  are  those  of  an  inflammatory  nature, 
although  until  recently  they  have  failed  to  receive,  both 
from  clinicians  and  pathologists,  that  recognition  which 
their  importance  deserves.  The  association  of  diabetes 
with  inflammatory  changes,  and  their  sequelcB,  have  in  a 
similar  way  been  largely  overlooked,  or  the  disease  has 
been  referred  to  some  other  cause.  As  we  have  seen,  the 
special  form  of  atrophy  described  by  Hansemann  is  in 
reality  a  fibrosis  due  to  inflammatory  changes  in  the  gland ; 
calculi  and  cysts  are  also  probably  not  responsible  for  the 
glycosuria  with  which  they  are  associated,  but  occur  in  the 
course  of  a  chronic  inflammation  which  ultimately  destroys 
the  structure  of  the  gland,  and  some  cases,  at  least,  of 
diabetes  associated  with  malignant  disease  of  the  pancreas 
are  caused  by  the  changes  brought  about  by  secondary 
inflammation.  Dieckhoff  in  his  analysis  of  fifty-three 
cases  found  acute  pancreatitis  in  10  per  cent,  and  chronic 
pancreatitis  in  36  per  cent.  Williamson  met  with  four 
instances   of  cirrhosis   of  the  pancreas  in  twenty-three 


Diabetes  287 

cases,  and  Opie  with  four  of  chronic  inflammation  in 
nineteen  cases,  so  that  it  is  probable  that  inflammatory 
changes  play  a  not  unimportant  part  in  the  production  of 
the  disease,  especially  if  the  different  manifestations  to 
which  reference  has  been  made  are  taken  into  account. 

Acute  pancreatitis  is  not  itself  a  common  disease,  and  is 
for  this  reason  alone  not  frequently  met  with  as  a  cause 
of  diabetes.  In  the  one  hundred  and  eighty-eight  cases 
collected  by  Oser  there  were  three  in  which  diabetes  was 
associated  with  hemorrhage  into  the  pancreas,  three  of 
necrosis  of  the  gland,  and  six  of  abscess;  yet  in  about 
one  hundred  cases  of  acute  inflammation,  collected  by 
Fitz  and  by  Seitz,  diabetes  was  only  present  in  two. 
The  reason  for  the  comparative  rarity  with  which  glyco- 
suria occurs  in  acute  pancreatitis  appears  to  be  that  when 
the  whole  organ  is  destroyed  death  usually  follows  very 
rapidly,  and  when  the  progress  of  the  disease  is  less  acute 
portions  of  the  gland  are  left  unaffected.  The  experi- 
ments of  Guleke  on  dogs  have  shown  that,  when  complete 
necrosis  of  the  pancreas  has  been  induced,  by  injecting 
oil  into  the  ligatured  pancreatic  duct,  glycosuria  always 
occurs,  but  that  when  a  portion  of  the  pancreas  has  been 
left  intact  no  sugar  can  be  found  in  the  urine.  This 
observer  also  found  that  in  animals  where  chronic  pan- 
creatitis had  been  produced  by  the  same  means  glycosuria 
was  present  in  some  and  not  in  others. 

A  case  of  haemorrhage  into  the  pancreas,  causing  destruc- 
tion of  the  whole  gland,  and  associated  with  the  appear- 
ance of  sugar  in  the  urine,  is  described  by  Bosanquet  in  his 
Goulstonian  lectures.  The  patient,  a  laundress  aged  fifty- 
three,  was  admitted  into  Charing  Cross  Hospital,  under  the 
care  of  Dr.  J.  M.  Bruce,  on  January  24,  1893.  A  week  be- 
fore she  had  been  seized  with  pain  in  the  abdomen,  which 
rapidly  swelled  and  became  hard  to  the  touch.  She  had 
previously  had  no  symptoms  of  diabetes,  but  then  com- 
plained of  thirst,  and  on  examining  the  urine  it  was  found 


288       The  Pancreas:  Its  Surgery  and  Pathology 

to  contain  from  10.12  to  11.25  grains  of  sugar  in  the 
twenty-four  hours.  Her  temperature,  which  on  the  24th 
was  100°  P.,  gradually  rose,  and  on  the  29th  and  30th  she 
had  rigors.  On  the  latter  day  acetone  was  present  in  the 
urine.  Finally  she  died  in  collapse  without  any  appear- 
ance of  coma.  At  the  necropsy  the  layers  of  the  mesen- 
tery were  everywhere  separated  by  a  large  mass  of  disin- 
tegrated blood-clot  and  blood-stained  fluid.  The  stomach 
was  adherent  to  the  left  lobe  of  the  liver,  and,  on  separat- 
ing the  two,  several  pints  of  blood-stained  grumous  fluid 
escaped.  In  the  situation  of  the  pancreas  was  a  break- 
ing-down mass  of  tissue,  along  with  much  bloody  fluid. 
There  was  also  diffuse  fat  necrosis  and  evidence  of  recent 
peritonitis.  Such  a  case  constitutes  a  natural  experi- 
ment on  the  removal  of  the  pancreas  in  a  human  being, 
and,  as  Bosanquet  points  out,  the  results  exactly  corre- 
spond to  those  obtained  in  animals. 

An  example  of  the  association  of  glycosuria  with  acute 
pancreatitis  in  which  recovery  took  place  has  been  re- 
corded by  Gifford  Nash,  in  the  "Lancet"  of  November 
II,  1902.  The  patient  was  a  man  of  sixty,  who  for 
seven  years  had  suffered  from  "bilious  attacks"  and  dis- 
comfort at  the  pit  of  the  stomach.  On  October  27,  1901, 
he  was  seized  with  sudden  pain  in  the  abdomen.  There 
was  no  jaundice,  and  the  symptoms  suggested  intestinal 
obstruction.  The  urine  was  increased  in  amount,  and 
contained,  on  November  5th,  8.75  grains  of  sugar  to  the 
ounce.  Operation  was  undertaken  on  November  17th. 
The  pancreas  was  found  to  be  enlarged,  there  was  fat 
necrosis  in  the  neighbourhood  of  the  gland,  and  a  large 
calculus  was  found  in  the  gall-bladder.  Cholecystotomy 
was  performed  and  the  patient  slowly  recovered.  On 
December  28th  the  urine  contained  4.5  grains  of  sugar 
per  ounce;  on  March  ist,  1902,  4.5  grains  also,  but  on 
May  17th  the  glycosuria  had  disappeared.  Through 
the  kindness  of  Dr.  Gifford  Nash  and  Dr.  J.  Tait,  we  were 


Diabetes 


289 


able  to  examine  a  specimen  of  the  patient's  urine  in 
November,  1902,  and  found  that  the  glycosuria  had  re- 
turned. A  well-marked  "pancreatic"  reaction  was  also 
obtained.  A  second  specimen,  examined  on  February  2, 
1904,  gave  similar  results.  It  was  then  stated  that  the 
patient  was  in  very  good  health,  and  had  had  no  illness 
since  the  operation.  In  January,  1906,  a  further  exami- 
nation was  made,  and  the  urine  was  found  to  contain 
0.95  per  cent,  of  sugar.  No  acetone  or  diacetic  acid  was 
present,  but  it  still  gave  a  positive  "pancreatic"  reaction. 

Chronic  interstitial 
pancreatitis  has  been 
frequently  observed  in 
association  with  dia- 
betes, but  in  the  ma- 
jority of  cases  where 
interstitial  changes  in 
the  pancreas  arise 
from  obstruction  of 
the  ducts  by  gall- 
stones, or  from  other 
causes,  glycosuria  is 
not  met  with  as  a 
symptom.  In  sixty- 
five  consecutive  cases, 
where  biliary  calculi 
were  found  in  the  common  duct  at  operation  and  the 
pancreas  was  enlarged  and  hard,  we  have  detected  sugar 
in  the  urine  of  four  (16  per  cent.).  In  three  of  these  the 
amount  was  under  0.2  per  cent.,  and  in  the  fourth  0.4  per 
cent,  was  present.  After  operation  the  sugar  disappeared 
from  the  urine  in  all  but  the  last,  in  which  it  slowly  in- 
creased in  amount,  the  patient  dying  from  diabetic  coma 
ten  months  subsequently.  Since  the  interstitial  changes 
arising  from  the  presence  of  gall-stones  in  the  common 
duct  principally  affect  the  head  of  the  gland  in  the  first 
19 


^s»^^r-- 


Fig.  107. — Spheroidal-celled  carcin- 
oma of  the  pancreas,  islands  of  Langer- 
hans  not  affected,  no  glycosuria  (X  40). 


290       The  Pancreas:  Its  Surgery  and  Pathology 

instance,  and  the  results  of  experiments  upon  animals 
have  shown  that  even  a  small  portion  of  healthy  pancrea- 
tic tissue  will  prevent  the  onset  of  diabetes,  or  at  least 
delay  the  appearance  of  the  symptoms,  so  long  as  it 
remains  undestroyed  by  fibrotic  changes,  the  comparative 


Fig.  108. — Chronic  interstitial  pancreatitis  following  duct  obstruc- 
tion, from  carcinoma  of  the  duodenum,  showing  islands  of  Langerhans 
unchanged  though  embedded  in  sclerotic  tissue;   no  glycosuria  (Opie). 


rarity  of  glycosuria  in  these  cases  is  not  difficult  to  ex- 
plain. When,  however,  a  great  part  of  the  parenchyma 
has  been  destroyed,  or  is  functionally  impaired,  by  the 
progressive  changes  consequent  on  repeated  or  long- 
continued  irritation,  either  from  gall-stones  or  an  unre- 


Diabetes 


291 


Fig.  109. — Section  of  the  pancreas 
from  a  case  of  diabetes  following  gall- 
stone obstruction  (X  42). 


lieved  duodenal  catarrh,  sugar  will  make  its  appearance 
in  the  urine,  first  as  an  alimentary  glycosuria,  and  later 
as  a  permanent  dia- 
betes. 

Some  observers 
have  attempted  to 
define  a  particular 
type  of  pancreatitis 
associated  with  dia- 
betes. Hoppe-Seyler 
and  Fleiner  have  de- 
scribed cases  of  the 
disease  accompany- 
ing general  arterial 
sclerosis,  and  Bosan- 
quet  in  two  out  of 
seven  cases  he  inves- 
tigated found  arterio- 
sclerosis, accompanied,  in  one  instance  in  which  the  glyco- 
suria had  been  intermittent,   by  gangrene   of  the  leg. 

Bosanquet  suggests  that- 
in  the  last  mentioned 
case  the  appearance  and 
disappearance  of  the 
sugar  might  be  due  to 
intermittent  pancreatic 
failure,  analogous  to  the 
"intermittent  claudica- 
tion ' '  sometimes  met 
with  in  arteriosclerosis. 
Lemoine  and  Lannois 
thought  that  the  new- 
growth  of  fibrous  tissue 
originated  in  the  peri- 
vascular tissue,  whence 
it   spreads   into  the   parenchyma.      In  four  cases  they 


■^  1>J 


*-i^ 


Fig.  no.  — Chronic  interstitial 
pancreatitis  with  arteriosclerosis, 
from  a  case  of  diabetes  (X  40). 


292       The  Pancreas:  Its  Surgery  and  Pathology 

examined,  they  described  the  penetration  of  fibrous  bands 
into  the  acini,  separating  the  cells  and  giving  rise  to  a 
unicellular  sclerosis. 

Opie  considers  that  diabetes  is  peculiarly  related  to 
interacinar  pancreatitis  and  that  in  the  interlobular  form 
it  is  rare.  The  difference,  he  considers,  depends  upon  the 
relation  of  the  fibrous  tissue  overgrowth  to  the  islands  of 
Langerhans,  which  he,  in  common  with  many  other 
observers,  believes  are  responsible  for  the  elaboration 
of  the  internal  secretion  by  means  of  which  the  pancreas 
exerts  its  influence  upon  carbohydrate  metabolism.  The 
newly  formed  fibrous  tissue  in  interacinar  pancreatitis 
is  diffusely  distributed  within  the  lobules  and  between 
the  individual  acini,  so  that  the  islands  are  affected  at 
the  same  time  as  the  other  elements  of  the  gland,  but  in 
the  interlobular  form,  which  is  the  type  following  duct- 
obstruction,  the  proliferation  of  fibrous  tissue  takes  place 
between  the  lobules  and  invades  them  from  the  periphery, 
so  that  the  cell  islets  suffer  only  when  the  process  is  far 
advanced,  and  the  secreting  parenchyma  has  been  re- 
placed by  masses  of  scar-like  tissue.  Opie  found  that 
diabetes  was  present  in  seven  out  of  nine  cases  of  inter- 
acinous  pancreatitis,  but  that  in  only  one  out  of  twenty- 
one  cases  of  chronic  interlobular  inflammation  of  the 
gland  was  there  sugar  in  the  urine.  In  this  one  case  of 
interlobular  inflammation  the  induration  of  the  gland 
was  far  advanced  and  the  islands  of  Langerhans  were 
fibroid.  The  two  cases  of  interacinous  pancreatitis  in 
which  diabetes  was  absent  were  both,  he  found,  in  an 
early  stage  of  the  disease. 

The  suggestion  that  the  islands  of  Langerhans  are 
concerned  in  the  production  of  the  "internal  secretion" 
of  the  pancreas  was  first  made  by  Laguesse.  This  view 
was  subsequently  adopted  by  Schafer,  Diamare,  and 
others.  The  theory  that  such  a  relationship  exists  is 
based  partly  on  histological  grounds,  and  partly  upon  the 


Diabetes  293 

results  of  experimental  work,  but  the  most  important 
evidence  in  support  of  it  has  been  furnished  by  patho- 
logical observations,  which  suggest  that  pancreatic  diabetes 
is  due  to  a  disturbance  of  the  functions  of  the  cell  islets. 
The  peculiarity  of  their  structure,  their  independence  of 
the  duct  system  of  the  gland,  and  their  comparative 
resistance  to  certain  morbid  changes  by  which  the  secret- 
ing acini  are  destroyed,  point  to  their  being  independent 
organs  with  an  independent  function;  while  their  rich 
blood  supply  may  be  taken  to  indicate  that  they  are 
possibly  vascular  glands,  engaged  in  the  elaboration  of 
some  internal  secretion  which  is  poured  into  the  blood 
stream.  Ssobolew,  who  has  sought  by  experimental 
means  to  prove  the  relationship  of  the  islands  of  Langer- 
hans  to  carbohydrate  metabolism,  states  that  when 
animals  are  overfed  with  carbohydrates  the  granules, 
which  have  appeared  in  the  cells  during  hunger,  diminish 
in  number,  in  the  same  way  as  the  zymogen  granules 
of  the  secreting  cells  diminish  as  the  result  of  functional 
activity.  Intravenous  injections  of  sugar,  he  believes, 
bring  about  a  similar  result.  But  this  has  been  denied 
by  Schmidt,  who  also  failed  to  observe  any  change  on 
introducing  sugar  into  the  peritoneal  cavity  of  mice 
and  guinea-pigs.  Schulze,  however,  experimenting  with 
guinea-pigs,  has  confirmed  the  observations  made  by 
Ssobolew. 

Basing  her  experiments  upon  the  observation  of  Schulze, 
Ssobolew  and  others,  that  complete  atrophy  of  the 
glandular  acini  of  the  pancreas  is  caused  by  ligaturing 
the  duct,  while  the  islands  of  Langerhans  remain  un- 
changed, Lydia  De  Witt  has  attempted  to  isolate  the  cell 
islets  in  cats,  and  study  the  physiological  action  of  an 
extract  made  from  them.  She  found  that  the  changes 
in  the  glandular  parenchyma  were  much  the  same  as 
those  described  by  Ssobolew,  but  that  when  no  special 
effort  was  made  to  avoid  including  the  blood-vessels  in 


294       The  Pancreas:  Its  Surgery  and  Pathology 

the  Hgature,  the  islands,  as  well  as  the  gland  tissue,  some- 
times atrophied,  whereas  when  precautions  were  taken  to 
avoid  interfering  with  the  blood  supply  of  the  gland  the 
islands  were  well  preserved,  regardless  of  the  extent  of 
atrophy  of  the  gland  tissue.  No  sugar  was  found  in  the 
urine,  either  after  the  operation  or  just  before  death, 
but  in  three  out  of  four  cases  a  positive  "pancreatic" 
reaction  was  obtained  when  the  urine  was  examined 
shortly  before  the  animal  died.  To  test  the  physio- 
logical powers  of  the  atrophied  gland,  it  was  removed 
immediately  after  death,  extracted  with  glycerine  or 
water,  and  the  digestive  and  glycolytic  actions  of  the 
extracts  investigated.  In  seven  out  of  twenty  cases 
there  was  no  digestion  of  starch,  fibrin,  or  fat,  while  in 
several  others  the  digestive  action  was  very  much  weak- 
ened, the  diminution  and  absence  of  digestive  action 
being  apparently  proportionate  to  the  degree  of  atrophy 
of  the  glandular  tissue.  No  appreciable  weakening  of 
the  glycolytic,  or  activator,  power  of  the  extract,  as 
tested  by  Cohnheim's  method,  was  noticed  in  any  of  the 
cases,  even  when  the  glandular  tissue  had  undergone 
atrophic  changes.  The  results  of  these  experiments, 
although  suggestive,  and  tending  to  support  the  theory 
that  the  islands  of  Langerhans  manufacture  a  substance 
analogous  to  the  "  activator  principle"  of  Cohnheim  which 
favours  the  glycolytic  action  of  muscle  ferment,  were  not 
as  decisive  as  had  been  hoped,  for  the  isolation  of  the 
islands  was  not  always  complete,  and  it  was  found  diffi- 
cult to  obtain  from  the  cat's  pancreas  sufficient  extract 
to  make  many  satisfactory  tests. 

Rennie  has  carried  out  some  investigations  with  ex- 
tracts prepared  from  the  large  cell  islets,  dissected  out 
free  from  pancreatic  tissue,  met  with  in  Lophius  piscato- 
rius  and  Scorpoena  scropha,  and  found  that  they  had  no 
inverting  pOAver.  Diamare  and  Kuliabko  state,  however, 
that  some  inversion  takes  place  on  standing  for  forty- 


Diabetes  295 

eight  hours.  The  latter  have  also  shown  that  the  extract 
has  no  digestive  power  for  starch,  whereas  an  extract 
made  from  the  pancreas  of  the  same  fish  rapidly  converts 
starch  into  sugar. 

The  pathological  changes  that  have  been  met  with  in 
the  interacinar  islets  in  cases  of  diabetes  are  hyaline  de- 
generation, necrosis,  atrophy  with  vacuolisation  and 
liquefaction  of  the  cell-protoplasm,  acute  and  chronic 
inflammation  with  haemorrhage,  sclerosis,  or  calcification, 
and  diminution  of  the  number  of  islets. 

Opie's  description  of  hyaline  degeneration  in  the  islands 
of  Langerhans  alone,  in  diabetes,  furnished  the  most  con- 
vincing evidence  of  the  association  of  these  structures 
with  carbohydrate  metabolism  up  to  that  time  available, 
and  from  the  publication  of  his  paper  in  1901  may  be 
dated  a  revival  of  interest  in  the  pancreatic  theory  of 
diabetes,  and  a  more  searching  and  minute  inquiry  on 
the  part  of  other  observers  into  the  condition  of  the  cell 
islets  in  fatal  cases  coming  to  post-mortem.  In  nineteen 
cases  of  diabetes,  in  which  Opie  investigated  the  condition 
of  the  islands  of  Langerhans,  he  found  hyaline  degenera- 
tion in  seven  (35  per  cent.).  The  first  example  of  the 
lesion  that  came  under  his  observation  w^as  in  a  severe 
case  of  diabetes.  The  islands  were^so  completely  altered 
as  to  be  unrecognisable,  and  the  secreting  parenchyma 
was  also  in  great  part  destroyed.  In  subsequent  cases  of 
his  series  the  relationship  of  the  diabetes  to  the  lesion  in 
the  islands  was  more  conclusively  demonstrated,  for, 
although  these  structures  had  undergone  very  grave  alter- 
ations, and  were  often  converted  into  almost  homogene- 
ous masses  of  hyaline  material,  the  secreting  parenchyma 
showed  in  some  instances  only  insignificant  changes,  and 
in  parts  of  the  gland  was  unchanged. 

Other  observers,  including  Wright  and  Joslin  (two  cases 
with  only  very  slight  alterations  of  the  glandular  acini) , 
Herzog  (one  with  slight  chronic  interstitial  infiammation) , 


296       The  Pancreas:  Its  Surgery  and  Pathology 


Fig.  III. — Sections  of  the  pancreas  from  a  case  of  diabetes  showing 
sclerosis  of  the  capsule  of  the  islands  of  Langerhans:  a,  Low  power; 
b,  the  same  islet  under  higher  magnification  (Gaylord  and  Aschoff). 


Diabetes  297 

Schmidt  (one  with  no  lesion  of  the  parenchyma),  and 
Lepine  (one  with  recent  fibrosis),  have  met  with  a  similar 
condition,  but  it  would  not  appear  to  be  as  common  as 
Opie's  experience  would  suggest.  Bosanquet  has  pointed 
out  that  the  possibility  of  the  degeneration  being  a  secon- 
dary change  in  diabetes  has  not  been  excluded.  He 
quotes  a  case  in  which  he  found  it  apart  from  diabetes 
in  association  with  extensive  arteriosclerosis  of  the  pan- 
creatic vessels,  in  a  woman  who  died  after  an  operation 
for  gall-stones. 

According  to  Weichselbaum  and  Stangl,  who  have 
studied  the  islands  of  Langerhans  in  thirty-five  cases  of 
diabetes,  the  lesion  most  frequently  met  with  is  simple 
atrophy  of  the  cells  together  with  vacuolisation  and  lique- 
faction of  the  cell-protoplasm.  Sclerosis  of  the  cell  islets 
was  only  met  with  in  four  out  of  their  second  series  of 
seventeen  cases.  Herzog  has  studied  three  cases  of 
diabetes  in  which  the  islands  were  the  seat  of  marked 
sclerotic  changes,  and  Schmidt  has  met  w4th  two  in  which 
there  was  interacinar  pancreatitis  so  seriously  involving 
the  cell  islets  that  many  of  them  were  converted  into 
connective- tissue  balls  resembling  fibrosed  glomeruli, 
as  they  were  also  in  one  of  Herzog 's  cases.  In  a  case 
reported  by  Lepine  the  islands  were  surrounded,  and  in 
places  partly  destroyed,  by  a  new-growth  of  fibrous  tissue. 
Gentes  has  also  described  a  case  of  diabetes  with  chronic 
interstitial  pancreatitis  invading  the  islands  of  Langer- 
hans. An  acute  inflammation,  limited  to  the  cell  islets, 
was  met  with  by  Schmidt  in  the  case  of  a  child  of  ten 
whose  urine  contained  6.8  per  cent,  of  sugar,  and  focal 
necrosis  of  the  pancreas  involving  the  islands  of  Langer- 
hans was  seen  by  Opie  in  one  case. 

Absence  of  the  islands,  or  diminution  of  their  number, 
has  been  reported  by  several  observers.  Ssobolew  failed 
to  find  them  in  six  cases  of  diabetes,  and  stated  that  in 
nine  others  they  were  abnormally  few.     Herzog  found  a 


298       The  Pancreas:  Its  Surgery  and  Pathology 


diminished  number  in  three  out  of  five  cases.  Weichsel- 
baum  and  Stangl  reached  the  conclusion  that  the  number 
of  islands  may  be  diminished  in  diabetes,  and,  since  the 
pancreas  is  almost  always  atrophic,  the  total  number  is 
still  further  curtailed.  Opie,  however,  points  out  that 
the  distribution  of  the  islands  varies  in  different  parts  of 
the  gland,  and  that,  while  they  may  be  almost  absent  in 
some  parts,  thqy  may  be  numerous  in  others,  and  partic- 
ularly in  the  tail  of  the  organ.      Before  arriving  at  any 

conclusion  as  to  the 
relative  number  of 
islands  in  any  portion 
of  the  pancreas,  it  is, 
therefore,  necessary  to 
compare  it  with  sec- 
tions prepared  from 
corresponding  parts  of 
the  gland  from  nor- 
mal individuals  of  the 
same  age.  This  condi- 
tion appears  to  have 
been  fulfilled  by 
Weichselbaum  and 
Stangl,  but  they  did 
not,  however,  separate 
cases  in  which  the 
islands  showed  lesions  from  those  in  which  they  were 
apparently  normal.  Opie  has  compared  the  size  and 
distribution  of  the  cell  islets  in  the  head,  body,  and  tail 
of  the  pancreas  in  eight  cases  of  diabetes,  and  found  that 
the  figures  obtained  showed  no  constant  departure  from 
the  normal.  A  striking  diminution  in  the  number  of 
islets  was  seen  in  two  cases,  and  in  one  of  these,  a  child 
of  fourteen  in  whom  the  diabetes  was  hereditary,  he  sug- 
gests that  it  might  be  due  to  a  congenital  defect  of  the 
gland.    He  concludes  that  "  while  diminution  in  the  size  of 


Fig.  112. — Chronic  interstitial  pan- 
creatitis with  fibrosis  of  the  islands  of 
Langerhans  from  a  case  of  diabetes  (X 
40). 


Diabetes  299 

the  gland,  together  with  absolute  and  relative  diminution 
in  the  number  of  interacinar  islands,  may  occasionally 
explain  the  occurrence  of  diabetes,  with  our  present 
knowledge  it  is  unjustifiable  to  assume  the  existence  of 
such  functional  deficiency  when  no  lesion  can  be  demon- 
strated by  the  methods  at  our  disposal." 

Most  of  the  published  cases  of  diabetes  in  which  the 
condition  of  the  islands  of  Langerhans  is  reported  have 
been  collected  by  Sauerbeck.  He  found  that  in  one  hun- 
dred and  seventeen  out  of  one  hundred  and  fifty-seven 
there  was  some  abnormality.  If  the  purely  quantitative 
changes  are  rejected,  as  being  of  too  indefinitive  a  char- 
acter, there  remain  ninety-eight  (62  per  cent.)  in  which 
qualitative  changes  were  observed. 

Most  modern  observers,  who  have  systematically 
investigated  the  islands  of  Langerhans  in  diabetes,  have 
eith,er  accepted  the  view  that  there  is  a  causal  relation- 
ship between  the  disease  and  lesions  of  the  islands,  or 
suspended  judgment  until  further  evidence  is  available. 
Hansemann,  however,  definitely  states  his  conviction  that 
no  such  relationship  exists.  He  investigated  thirty-four 
cases,  and  found  that  the  islands  were  present  in  all. 
In  some,  where  nearly  the  whole  parenchyma  had  been 
destroyed  by  fat  or  interstitial  fibrosis,  he  states  that, 
although  they  were  diminished  in  number,  they  were 
unchanged.  In  six  cases  he  found  the  islands  invaded  by 
what  he  regards  as  hyaline  connective  tissue,  but  since 
they  were  not  all  affected  and  there  was  an  accompany- 
ing interstitial  fibrosis  of  the  gland,  it  appeared  to  be  a 
matter  of  chance  whether  the  islands  were  involved  or 
not,  but  he  admits  that  he  has  not  met  wdth  a  case  in 
which  fibrosis  affected  the  islands  without  diabetes  being 
present. 

Chauft'ard  and  Ravant  met  with  swelling  and  increase 
of  size  in  the  islands  of  Langerhans,  without  glycosuria, 
in  thirteen  cases  of  enteric  fever,  two  of  pneumonia,  and 


300       The  Pancreas:  Its  Surgery  and  Pathology 

one  of  erysipelas.  They  do  not  regard  the  condition  as 
pathological,  however,  but  consider  it  as  a  hypertrophic 
reaction.  Salisbury  Trevor  observed  similar  changes  in 
the  cell  islets  in  pneumonia  and  infective  endocarditis. 

Herxheimer,  studying  the  cell  islets  in  the  cirrhotic 
pancreas  so  often  found  in  diabetes,  states  that  he 
found  evidence  of  their  new  formation  from  the  small 
ducts,  but  he  regards  the  whole  pancreas  as  controlling 
sugar  metabolism,  and  thinks  that  diabetes  is  due  to 
a  functional  lesion  of  the  gland,  which  may  or  not  be 
accompanied  by  visible  morbid  changes.  In  man  he 
considers  that  the  islets  alone  are  inadequate  for  the 
prevention  of  diabetes,  while  in  animals  they  appear  to  be 
sufficient.  This  statement  is,  however,  not  supported 
by  any  convincing  evidence,  and  is  in  fact  directly  con- 
troverted, as  regards  human  diabetes,  by  a  case  described 
by  S.  G.  Scott,  in  which,  although  only  the  islands  of 
Langerhans  remained,  no  trace  of  sugar  was  found  in 
the  urine. 

Even  if  the  connection  of  the  islands  of  Langerhans 
with  diabetes  is  granted,  a  certain  number  of  cases  remain 
in  which  no  lesion  whatever  of  the  pancreas  has  been  dis- 
covered by  competent  observers.  Opie  met  with  four 
in  his  nineteen  cases.  Williamson  eight  in  twenty-two, 
Ssobolew  two  in  fifteen,  and  in  twenty- three  examined 
by  Schmidt  there  was  no  change  in  eight,  and  in  eight 
others  the  alterations  were  so  slight  as  to  be  considered 
secondary  to  the  diabetic  condition.  It  may  be  contended 
that  the  specific  diabetic  disturbances  of  the  pancreas 
are  not  necessarily  connected  with  visible  anatomical 
alterations  of  the  islets,  or  in  any  other  tissue  of  the  gland, 
and,  although  it  is  possible  that  in  some  instances  there 
may  be  minute  alterations  in  the  molecular  arrangement 
of  the  cells  which  cannot  be  discovered  with  the  micro- 
scope, we  are  at  present  unacquainted  with  any  other 
method  of  demonstrating  minute  morbid  changes,   and 


Diabetes  301 

most  perforce  aV)i(le  by  the  results  obtainable  by  the 
means  at  our  disposal.  It  is  ^jossible,  however,  that  at 
the  present  time  we  include  under  the  term  diabetes  several 
conditions,  having  somewhat  similar  symptoms,  and  all 
characterised  by  the  presence  of  glycosuria,  which  are 
not  due  to  the  same  cause.  There  is  no  doubt  that  those 
in  which  lesions  of  the  pancreas  are  present  form  a  larger 
class  than  is  generally  supposed,  but  it  may  prove  that 
diseases  of  other  organs  or  tissues  are  responsible  for 
some,  and  that  the  cases  in  which  the  pancreas  appears 
to  be  normal  after  death  have  a  separate  origin.  At  the 
same  time  it  is  well  to  bear  in  mind,  as  von  Noorden  has 
insisted,  that  scientific  medicine  has  been  so  long  under 
the  influence  of  morbid  anatomy  that  it  is  often  difficult 
to  realise  that  important  disturbances  of  function  may 
occur  when  microscopical  examination  reveals  no  dis- 
tinctive pathological  changes. 

The  association  of  arteriosclerosis,  gout,  syphilis,  and 
alcoholism  with  diabetes  is  probably  to  be  explained  by 
the  fibrotic  and  degenerative  changes  which  each  is 
capable  of  setting  up  in  the  pancreas.  Cirrhosis  of  the 
liver  is  often  found  to  coexist  with  chronic  interstitial 
pancreatitis  in  diabetes,  and  both  probably  originate 
from  the  same  causes.  The  apparently  infective  cases  of 
diabetes  may  be  due  to  the  effects  produced  upon  the  pan- 
creas by  the  entry  of  micro-organisms  from  the  duodenum, 
and  the  history  of  digestive  disturbances,  which  is  not 
uncommon  in  diabetes,  suggests  that  a  chronic  duodenal 
and  gastric  catarrh  may  in  some  instances  give  rise  to  the 
conditions  favourable  for  the  onset  of  a  pancreatic  lesion. 
Chronic  pancreatitis  has  been  repeatedly  observed  in 
association  with  acromegaly,  and  it  appears  probable  the 
diabetes,  transient  glycosuria,  and  alimentary  glycosuria 
that  have  been  seen,  not  infrequently,  to  accompany  this 
disease  are  to  be  referred  to  pathological  changes  in  the 
pancreas. 


302       The  Pancreas:  Its  Surgery  and  Pathology 

We  have  seen  that  painting  the  pancreas  with  adrenaHn, 
and  a  variety  of  other  substances,  gives  rise  to  glycosuria, 
but  that  the  action  of  the  suprarenal  extract  appears  to  be 
of  a  specific  and  peculiar  nature.  Blum  has  produced 
temporary  glycosuria  by  injecting  suprarenal  extract  into 
the  veins  and  subcutaneous  tissues  of  animals,  and  the 
same  result,  but  to  a  more  marked  degree,  has  been  found 
by  Herter  and  Richards  to  follow  injections  of  adrenalin 
into  the  peritoneal  cavity.  These  experiments  suggest  that 
there  is  some  connection  between  the  glycolytic  action  of 
the  pancreas  and  the  suprarenal  bodies,  and  the  anatomi- 
cal picture  presented  by  cases  of  so-called  "diabete  bronze" 
tends  to  favour  this  view. 

Bronzed  diabetes  is  closely  related  to  the  condition  de- 
scribed by  von  Recklinghausen  under  the  name  of  hsemo- 
chromatosis,  in  which  the  epithelial  cells  of  the  various 
glands  of  the  body,  and  particularly  of  the  pancreas  and 
liver,  show  deposits  of  a  reddish-yellow  iron-containing 
pigment,  the  smooth  muscle-fibres  of  the  blood-  and 
lymph -vessels,  and  of  the  walls  of  the  gastro-intestinal 
tract,  contain  fine  granules  of  a  bright  yellow,  iron-free 
pigment,  and  there  is  hypertrophic  cirrhosis  of  the  liver, 
but,  unlike  simple  hasmochromatosis,  it  is  associated  with 
a  rapidly  fatal  form  of  diabetes  mellitus.  Although 
bronzing  of  the  skin  is  present  in  the  majority  of  cases, 
it  is  not  constant.  When  present  it  is  usually  general 
and  uniform,  but  is  not  accompanied  by  pigmentation  of 
the  mucous  membranes,  as  in  Addison's  disease. 

Hanot  and  Chauffard,  who  first  described  the  condi- 
tion in  1882,  found,  in  one  of  their  cases,  of  which  they 
made  a  careful  study,  that  there  was  advanced  chronic 
interstitial  pancreatitis,  and  other  observers,  who  have 
had  the  opportunity  of  investigating  the  disease,  have 
also  found  that  the  pancreas  was  affected.  Where  a 
microscopical  examination  of  the  gland  has  been  made 
interstitial  fibrosis  has  been  found,  the  connective-tissue 


Diabetes  303 

spaces  being  much  enlarged,  and  they,  as  well  as  the  cells, 
have  contained  a  deposit  of  reddish-yellow  f)igiTient. 
Margain  has  recently  reported  that,  in  a  fatal  case  of 
bronzed  diabetes  he  examined,  some  of  the  islands  of 
Langerhans  were  preserved,  but  that  their  cells  were 
crowded  with  pigment.  Hanot  and  Chauffard  believed 
that  the  diabetes  was  the  primary  factor  in  the  disease, 
the  changes  in  the  liver  and  other  tissues  being  due  to 
diabetic  alterations  in  the  blood,  and  to  the  accompany- 
ing endarteritis,  but  Marie  Acard,  Dutourier  and  Jeanselme, 
and  Anschiiltz  think  that  the  tissue  changes  result 
from  a  deposit  of  pigment  in  them,  and  that  the  pigment 
arises  from  a  dissolution  of  haemoglobin  from  some  un- 
known cause.  According  to  this  view,  the  diabetes  is  a 
secondary  phenomenon  due  to  the  changes  in  the  pancreas. 
Opie,  who  has  examined  a  case  of  haemochromatosis,  is 
of  opinion  that  it  is  a  distinct  morbid  entity,  associated 
with  chronic  interstitial  inflammation,  notably  of  the 
liver  and  pancreas,  and  that,  when  the  pancreatitis  has 
reached  a  certain  grade  of  intensity,  diabetes  mellitus 
ensues,  and  is  usually  the  terminal  event.  He  finds  that 
the  pancreatic  inflammation  is  of  the  interacinar  type,  and 
that  the  islands  of  Langerhans  are  implicated  in  the  lesion. 
A  few  cases  have  been  described  in  which  there  has  been 
no  glycosuria,  although  the  whole  of  the  pancreas  has 
been  apparently  destroyed  by  malignant  disease  or  inflam- 
matory processes,  but  none  are  of  recent  date,  and  in 
most  instances  the  proof  of  total  destruction  rests  upon 
macroscopical  examination  alone.  In  view  of  the  abun- 
dant experimental  and  clinical  evidence  now  available, 
that  the  pancreas  is  essential  for  carbohydrate  metabo- 
lism, the  proof  that  its  absence  can  be  unattended  by 
glycosuria  must  be  exceptionally  strong,  although  it 
must  be  admitted  that  a  single  well  authenticated  in- 
stance would  call  for  a  revision  of  the  views  at  present 
generally  held. 


304       The  Pancreas:  Its  Surgery  and  Pathology 

Minkowski,  as  we  have  seen,  showed  that  if  only  part 
of  the  pancreas  be  removed  in  animals  diabetes  does  not 
result,  but  the  ability  of  the  organism  to  perform  its  nor- 
mal functions  in  carbohydrate  metabolism  is  impaired, 
so  that  large  doses  of  sugar  give  rise  to  temporary  glyco- 
suria. The  capacity  of  the  body  to  deal  with  carbohy- 
drates is  normally  limited,  and  is  not  the  same  for  all 
varieties  of  sugar.  Glucose  appears  to  have  the  highest 
limit  (150  to  200  grams  in  one  dose),  tevulose  can  be 
taken  in  somewhat  similar  amounts  without  producing 
glycosuria  (140  to  160  grams  in  a  single  dose),  cane-sugar 
also  can  be  taken  in  doses  of  150  to  200  grams,  but  milk- 
sugar  has  a  much  lower  limit  (80  to  100  grams).  Accord- 
ing to  V.  Noorden,  the  assimilative  capacity  of  normal 
individuals  varies  very  considerably  for  maltose,  for  while 
there  are  some  who  can  tolerate  considerable  quantities, 
there  are  others  who  possess  a  very  low  assimilation  limit. 
According  to  him,  this  accounts  for  the  appearance  of 
sugar  in  the  urine  of  some  persons  after  even  a  moderate 
amount  of  beer  has  been  taken.  Pentoses  are  only 
assimilated  with  difficulty,  and  even  the  ingestion  of  so 
small  a  quantity  as  30  to  50  grams  is  followed  by  the 
appearance  of  almost  half  in  the  urine.  For  starch  no 
limit  is  known,  for  if  as  much  as  400  or  500  grams  are 
consumed  in  a  few  hours  alimentary  glycosuria  does  not 
occur. 

Pathologically  alimentary  glycosuria  occurs  in  certain 
nervous  and  brain  troubles,  in  diseases  of  the  liver,  and 
as  the  result  of  lesions  of  the  pancreas,  as  well  as  in  some 
cases  of  acute  febrile  disease,  and  in  acute  and  chronic 
alcoholic  intoxication.  The  glycosuria  met  with  in  the 
two  last  groups  has  been  attributed  to  disturbances  of 
the  liver,  but  v.  Noorden  considers  that  it  arises  from 
real,  though  transitory,  disturbances  of  the  pancreas, 
for  the  glycosuria  is  much  more  marked  than  is  that  met 
with  in  liver  disease,  the  influence  of  glucose  much  ex- 


Diabetes  305 

ceeds  that  of  laevulose,  whereas  in  liver  disease,  as  a  rule, 
the  organism  reacts  much  more  strongly  to  the  latter, 
and  glycosuria  can  be  produced  by  an  excess  of  starchy 
food. 

The  relation  of  the  pancreas  to  alimentary  glycosuria 
in  man  has  been  investigated  by  Willie,  who  gave  70  to 
100  grams  of  grape-sugar  to  eight  hundred  patients,  suf- 
fering from  a  variety  of  diseases,  in  the  morning  before 
food  had  been  taken.  The  urine  was  examined  before 
the  test,  and  at  intervals  of  two  hours  afterwards.  Of 
the  eight  hundred  individuals,  seventy-seven  subse- 
quently died  and  were  examined  post-mortem.  Alimen- 
tary glycosuria  had  been  found  in  fifteen  of  these,  and  in 
ten  there  were  present  grave  lesions  of  the  pancreas, 
either  primary,  or  secondary  to  growths  in  the  stomach, 
liver,  or  gall-bladder. 

Since  pancreatic  diabetes  presents  no  characteristic 
clinical  symptoms  by  which  it  can  be  recognised  with 
certainty,  its  treatment  differs  in  no  essential  respect 
from  that  by  which  it  is  sought  to  stay  the  progress  of 
diabetes  in  general.  Reliance  must  be  placed  mainly 
upon  diet  and  the  control  of  the  hygienic  condition  of 
the  patient.  Although  numerous  drugs  have  been  sup- 
posed to  have  a  beneficial  effect  in  cases  where  the  pan- 
creas was  believed  to  be  diseased,  there  is  no  evidence 
that  a  pancreatic  lesion  can  be  directly  controlled  by  this 
means,  except  possibly,  to  a  certain  extent,  by  mercury 
in  syphilitic  cases.  As  it  is  probable,  however,  that  some 
cases  of  pancreatic  diabetes  may  arise  from  an  infection 
reaching  the  gland  by  way  of  the  intestine,  drugs  calcu- 
lated to  allay  catarrh  of  the  duodenal  mucous  mem- 
brane and  control  the  intestinal  flora  may  be  of  some 
service  in  preventing  the  progress  of  the  disease.  It  is 
also  possible  that  gastro-enterostomy  and  cholecysten- 
terostomy,  by  draining  the  affected  areas  and  putting 
them  to  rest,  might  in  similar  cases  have  a  beneficial  effect. 


3o6       The  Pancreas:  Its  Surgery  and  Pathology 

The  satisfactory  results  following  the  administration 
of  thyroid  extract  in  myxoedema  and  sporadic  cretinism 
have  naturally  suggested  that  the  use  of  pancreatic 
extracts,  or  of  the  fresh  gland,  might  be  equally  effectual 
in  the  treatment  of  pancreatic  diabetes.  In  a  few  cases 
it  has  been  claimed  that  some  amelioration  of  the  symp- 
toms has  been  produced  in  this  way,  but  the  majority  of 
observers  are  agreed  that,  although  some  improvement 
in  the  digestive  powers  may  result,  the  glycosuria  and 
other  symptoms  of  the  diabetic  condition  are  unin- 
fluenced. In  order  to  avoid  destruction  of  the  ferments 
contained  in  the  extract  by  digestion  in  the  alimentary 
tract,  subcutaneous  injection  has  been  resorted  to,  but 
with  equally  unsatisfactory  results.  Clinical  experience, 
however,  in  these  respects  only  confirms  the  experimental 
results  obtained  by  Minkowski,  Thiroloix,  and  others, 
who  found  that  in  depancreatised  animals  the  administra- 
tion of  fresh  pancreas  or  pancreatic  extracts  by  the  mouth, 
subcutaneously,  into  the  peritoneum,  or  into  the  veins  had 
no  effect  in  controlling  the  glycosuria.  It  is  possible 
that  the  action  of  the  pancreas  in  carbohydrate  metabo- 
lism may  be  a  function  of  the  living  gland,  and  that,  for 
this  reason,  extracts  and  preparations  made  from  the 
dead  organ  may  fail  to  be  of  use  in  diabetes,  but  the 
subcutaneous  implantation  of  the  pancreas  of  the  lower 
animals  into  diabetics,  contrary  to  what  might  be  expected 
from  experimental  work  on  the  grafting  of  pancreatic 
tissue  beneath  an  animal's  own  skin  previous  to  extir- 
pating the  gland,  has  not  proved  of  any  service  as  a 
therapeutic  measure. 

Basing  their  treatment  on  the  effects  of  secretin  as  a 
stimulant  of  the  pancreas,  Moore,  Edie,  and  Abram  have 
employed  an  acid  extract  of  duodenal  mucous  membrane 
in  diabetes.  They  found  that,  when  this  was  given  by  the 
mouth,  the  sugar  in  the  urine  gradually  diminished  in  some 
cases,  and  finally  disappeared  in  a  few.    In  others,  although 


Diabetes  307 

there  was  an  improvement  in  the  digestion,  no  effect  on 
the  sugar  output  was  produced.  Bainbridge  and  Bed- 
dard,  however,  have  not  noticed  any  amelioration  of  the 
symptoms  in  cases  they  have  treated  by  this  method, 
and  suggest,  as  the  result  of  their  experience,  that  any 
improvement  that  takes  place  is  to  be  attributed  to  the 
diet  and  not  to  the  secretin.  J.  R.  Charles  has  also  failed 
to  notice  any  good  following  the  use  of  secretin  in  three 
cases  of  diabetes.  The  method  is,  as  yet,  in  an  experi- 
mental stage,  and  the  number  of  cases  in  which  it  has  been 
tried  are  too  few  to  prove  whether  it  is  really  efficacious 
in  genuine  cases  of  pancreatic  diabetes  or  not.  Even 
should  it  be  shown  eventually  that  acid  duodenal  extract 
can  exert  some  influence  in  controlling  glycostiria,  it  is 
open  to  question  whether  the  treatment  may  not,  in  the 
end,  do  more  harm  than  good,  for  the  artificial  stimtda- 
tion  of  the  diseased  tissue  that  may  remain  in  cases  of 
pancreatic  diabetes,  although  it  may  at  first  induce  in- 
creased activity,  is  likely  to  eventually  bring  about 
fatigue,  and  cause  more  rapid  degeneration  than  would 
have  occurred  if  it  had  been  let  alone.  The  intravenous 
injection  of  secretin  has  been  shown  by  Starling  to  give 
rise  to  acute  inflammation  of  the  intestines,  and  even  to 
gastric  ulcers,  in  animals,  for  the  pancreatic  juice  is  not 
met  and  neutralised  by  the  acid  gastric  contents  which 
normally  cause  the  flow.  This  objection  does  not  apply 
to  the  administration  of  secretin  by  the  mouth,  as  the 
secretion  will  be  gradual,  and  correspond  to  the  acidity 
of  the  gastric  juice  reaching  the  intestine. 

Cohnheim's  work  upon  the  effects  of  a  mixture  of  pan- 
creatic and  muscle  extracts  in  glycolysis  has  suggested 
the  use  of  such  a  mixture  in  diabetes,  and  it  has  been 
employed  for  this  purpose  by  Crofton. 

The  difficulty  that  attends  all  methods  of  treating 
diabetes  is  vastly  increased  by  the  obscurity  of  the  etiol- 
ogy, but  where  it  follows,  or  is  associated  with,  evidences 


3o8       The  Pancreas:  Its  Surgery  and  Pathology 

of  pancreatic  or  gall-stone  trouble,  the  origin  of  the  disease 
is  plain,  and,  in  the  early  stages,  appropriate  means  of 
treatment  can  be  adopted  with  a  fair  hope  of  success. 
We  have  already  referred  to  four  cases  of  cholelithiasis 
in  our  own  experience  that  were  accompanied  by  glyco- 
suria, and  in  three  of  which  operation  was  followed  by 
disappearance  of  sugar  from  the  urine.  Gifford  Nash's 
case  of  acute  pancreatitis  with  glycosuria  may  also  be 
cited  as  an  example  of  the  satisfactory  results  attending 
timely  operative  interference.  It  is  essential,  however, 
that  the  disease  should  not  be  too  far  advanced,  and  for 
this  reason  we  strongly  recommend  that  all  cases  of  pan- 
creatitis and  gall-stones  likely  to  give  rise  to  a  pan- 
creatic lesion  should  be  operated  on  with  as  little  delay 
as  possible  after  they  have  been  diagnosed.  As  we 
shall  show  in  a  subsequent  chapter,  the  early  recognition 
of  these  conditions  is  not  now  a  matter  of  great  difficulty, 
if  all  the  signs  and  symptoms  to  be  obtained  by  a  careful 
consideration  of  the  clinical  and  pathological  features  of 
the  case  are  taken  into  account,  so  that  difficulty  of  diag- 
nosis cannot  be  urged  as  a  valid  excuse  for  cases  of  pan- 
creatitis being  permitted  to  proceed  untreated  to  a  stage 
at  which  diabetes  supervenes. 

Literature 

Abram:   Lancet,  Jan.  27,  1906. 

Acard:   Thesis,  Paris,  1895. 

Aldehoff:  Zeitsch.  f.  Biol.,  xxviii,  293. 

Anschiitz:   Deutsch.  Arch.  f.  klin.  Med.,  1899,  Ixii,  411. 

Bainbridge  and  Beddard:    Bio-chemical  Journ.,  Sept.,   1906. 

Bloch:  Quoted  by  Oser,  Nothnagel's  "Encylop.  of  Pract.  Med." 

Blum:   Deutsch.  Arch.  f.  klin.  Med.,  190 1,  Ixxi,  146. 

Blumenthal:  Zeitsch.  f.  diatet.  u.  physik.  Therapie,  1898,  i,  250. 

Bosanquet:   Lancet,  1905,  i,  903. 

Bouchardat:   Compt.  rend,  acad.,  xx,  1085. 

Bright:   Med.  Assoc.  Trans.,  1833,  p.  18. 

Capparelli:   Arch.  ital.  de  Biol.,  1894,  xxi,  398. 

Charles,  J.  R. :   Bristol  Medico-Chirurg.  Journ.,  Sept.,  1906. 

Chauffard  and  Ravant:    Arch,  de  Med.  Exp.  et  d'Anat.  Path.,  March, 

1901,  p.   175. 
Chopart:     "Diabetes  with   Calculus   Formation,"    quoted  by   Klebs, 

P-  547- 


Diabetes  309 

Cohnheim:    Zeitsch.  f.  physiol.  Chem.,  1903,  xxxix,  336;    IVjid.,  1904, 

xlii,  401;     Ibid.,  1906,  xlvii,  253. 
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Crofton:    Amer.  Journ.  of  Med.  Sci.,  April,   1902.      Philadelphia  Med. 

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Dewitt:   Journ.  of  Exp.  Med.,  1906,  viii,  193. 

Diamare:    Internal.  Monatsschr.  f.  Anat.  u.  Phys.,  1899,  xvi,  155. 
Diamare  and  Kuliabho:   Zeit.  f.  Phys.,  xviii,  14. 
Dutourier:   Thesis,  Paris,  1895. 
Elliotson:    Med.  Chir.  Trans.,  1833,  xviii,  67. 
Fles:    Holland.  Arch.,  1864,  iii,  187. 
Fleiner;   Berliner  klin.  Woch.,  1894,  xxxi,  38. 

Frerichs:    "Leberkrankheiten,"   1858;     " Ueber  der  Diabetes,"   1884. 
Gentes:    Thesis,  Bordeaux,   1901. 
Guleke:  Archiv.  f.  klin.  Chirurgie,  Ixxxvii,  Heft  4. 
Hammerschlag  and  Kauffmann:  Quoted  by  Lenn6,  Therapeut.  Mon- 

atsch.,  1902,  S.  182. 
Hanot  and  Chauffard:    Rev.  de.  m^d.,  1882,  ii,  385. 
Harley:    Journ.  of  Anat.  and  Phys.,  1891,  p.  201;    Brit.  Med.  Journ., 

1892. 
Hartsen:  Arch.  f.  Holland.  Beitrage  z.  Naturheilkunde,  1884,  iii,  319. 
Hansemann:  Zeitschr.  f.  klin.  Med.,  1894,  S.  191 ;  Verhandl.  derDeutsch. 

path.  Gesellsch.,  1902,  iv,  187. 
Hedon:    "Physiol,  du  Pancreas,"  Paris. 
Herter  and  Richards:   Medical  News,  Feb.  i,  1902, 
Herxheimer:  Virchow's  Archiv.,  1906,  clxxxiii,  2. 
Herzog:   Virchow's  Archiv.,  1902,  clxviii,  Hft.  i,  83. 
Hoppe-Seyler:   Deutsches  Arch.  f.  klin.  Med.,  1893,  Iii,  171. 
Jeanselme:   Bull,  et  mem.  d.  h6p.  de  Paris,  1897,  ^^^'  ^79- 
Laguesse:   Compt  Rend.  Soc.  de.  Biol.,  1893. 
Lancereaux:   Bull.  acad.  de.  m6d.,  1877,  p.  1224. 
Lemoine  and  Lannois:  Arch,  de  m6d.  exp.,  1891,  iii,  33. 
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1903,  xliii,  623;    Journ.  de  Phys.  et  de  Path,  gen.,  1905,  vii,  i. 
Lorand:    Compt.  rend,  de  la  Soc.  de  Biol.,  1904,  Ivi,  488. 
Margain:   Rev.  de  Medecine,  March  10,  1905,  p.  214. 
Marie:   Semaine  m6d.,  1895,  xv,  229. 
Mering  and  Minkowski:    Klebs'  Arch.,  1899,  xxvi,  37;    Semaine  med., 

22  mai,  1889;  Arch.  f.  exper.  Path.  u.  Phar.,  1890,  xxvi,  371. 
Minkowski:     Berliner  klin.   Wochenschr.,    1890,   Nr.   8;    Centralbl.   f. 

Pathologie,  1892;   Arch.  f.  exper.  Path.  u.  Phar.,  1893,  xxxi,  85. 
Moore,  Edie,  and  Abram:   Bio.  Chemical  Journ.,  Sept.,  1906. 
Munk:   Tagebl.  der  43  Naturforscherversammlung,  1869,  S.  112. 
Nash,  Gifford:   Lancet,  November  11,  1902. 
Noorden:    "Diabetes  Mellitus,"  tr.  Boardman  Reed,  1906. 
Opie:   "Diseases  of  the  Pancreas,"  1903. 
Pavy:    "Carbohydrate  Metabolism  and  Diabetes." 
Recklinghausen:     Virchow's  Arch.,  1864,  xxx,  362;  Tageblatt  der  62 

Versamme.  deutsch.  Naturforsch.  u.  Aertze  in  Heidelberg,  1889, 
.  S.  324. 
Rennie:   Zent.  f.  Phys.,  1905,  xvii,  23. 
Sandmeyer:   Zeitsch.  f.  Biol.,  1895,  xxxi,  13. 
Sauerbeck:    Virchow's  Archiv,  1904,  clxxvii,  Suppl.  Heft  1;    Verhandl. 

der  deutsche  path.   Gesellsch.  Centralb.   f.   path.  Anat.,    1904, 

XV,  217. 
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Schmidt:   Munchener  med.  Woch.,  1902,  xlix,  51. 
Schulze:    Arch.  f.  mik.  Anat.,  1900,  Ivi,  491. 


3IO       The  Pancreas:  Its  Surgery  and  Pathology 

Seegen:    "Der  Diabetes  mellitus,"  Berlin,  1893. 

Silver:  Trans.  Path.  Soc,  1873,  xxiv;  Ibid.,  1878,  xxix. 

Ssobolew:    Virchow's  Arch.,  1902,  clxviii,  91;    Centralbl.  f.  allg.  Path. 

u.  path.  Anat.,  xi,  202. 
Starling:  Tr.  Path.  Soc,  Ivi,  255. 
Strauss:   Zeitsch.  f.  klin.  Medicin.,  xxvi,  27. 
Thiroloix:  Thesis,  Paris,  1892. 

Trevor,  Salisbury:    Practitioner,  April,  1904,  p.  574. 
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Ibid.,  1902,  XV,  969. 
Weintraud:   Arch.  f.  exp.  Pathol.,  xxxiv,  303. 
Williamson:   "Diabetes  Mellitus,"  1898. 
Windle:   Dublin  Journ.  of  Med.  Sci.,  1883. 
Wright  and  Joslin:  Journ.  of  Med.  Research,  1901,  i,  360. 


CHAPTER   XII 

GENERAL  SYMPTOMATOLOGY  AND  DIAGNOSIS 

The  varied  and  important  part  the  pancreas  takes  in 
the  digestive  processes  that  go  on  in  the  intestine,  and 
the  equally  important  influence  that  it  appears  to  exert 
upon  the  internal  metabolism  of  the  body,  would  natur- 
ally suggest  that  any  departure  from  the  normal  would 
lead  to  such  disturbances  of  function  that  the  symp- 
toms of  diseases  of  the  pancreas  would  be  so  marked  as 
to  make  the  diagnosis  easy.  But  this  is  far  from  being 
the  case  for  several  reasons:  First,  it  is  seldom  that  the 
pancreas  is  diseased  without  other  organs  also  being 
involved;  for  example,  pancreatitis  is  very  frequently 
associated  with  cholelithiasis;  gastro-intestinal  catarrh 
and  catarrh  of  the  bile  and  pancreatic  ducts  often  coexist ; 
ulcers  or  tumours  of  the  stomach  or  duodenum  may  extend 
to,  and  involve,  the  pancreas;  and  affections  of  the  liver, 
colon,  or  lymphatic  glands  may  give  rise  to  disease  in 
the  pancreas.  Secondly,  the  digestive  functions  of  the 
pancreas  can  be  carried  out,  more  or  less  completely,  by 
other  agencies,  the  stomach  can  deal  with  proteids,  the 
salivary  and  intestinal  glands  have  the  power  of  digesting 
starches,  and  the  bile  and  intestinal  secretions  can  emul- 
sify fat;  moreover,  the  intestinal  bacteria,  as  we  have 
seen,  possess  the  power  of  breaking  down  various  food 
materials,  and  so  interfering  with  the  pathological  altera- 
tions in  the  stools  that  might  be  expected  in  pancreatic 
diseases.  Thirdly,  a  considerable  portion  of  the  gland 
may  be  necrosed  and  cast  off,  or  otherwise  disabled,  and 
yet  the  remaining  portion  may  apparently  be  sufficient 
to  carry  on  the  functions  of  the  organ.     Fourthly,  in 

311 


312       The  Pancreas:  Its  Surgery  and  Pathology 

some  cases  the  pancreas  may  be  the  organ  primarily  at 
fault,  and  yet  the  most  prominent  symptoms  may  be 
caused  by  another  organ  that  is  involved  secondarily; 
for  instance,  cancer  of  the  head  of  the  pancreas  gives  rise 
to  intense  jaundice  and  distension  of  the  gall-bladder, 
suggesting  to  the  uninitiated  a  primary  affection  of  the 
liver  or  bile-ducts,  but  the  symptoms  are  in  reality  due  to 
gripping  of  the  common  bile-duct  by  the  growth,  and 
simple  chronic  pancreatitis  may  also  cause  jaundice  for 
the  same  reason.  Again,  a  tumour  of  the  pancreas  may 
compress  the  intestine  and  produce  intestinal  obstruction, 
or  may  press  upon  the  neighbouring  ganglia  and  cause 
most  violent  pain,  mimicking  that  met  with  in  spinal 
disease,  aneurysm,  etc.  Thus  it  will  be  seen  that  in 
diseases  of  the  pancreas  very  conflicting  combinations  of 
symptoms  may  arise,  which  may  lead  to  great  difficulty 
in  diagnosis,  unless  some  well-defined  guiding  principles 
can  be  established  by  which  it  may  be  determined,  with  a 
considerable  degree  of  certainty,  that  the  pancreas  is, 
or  is  not,  the  organ  primarily  at  fault.  This  we  hope  to 
show  is  not  impossible. 

The  signs  and  symptoms  which  are  present,  to  a  greater 
or  less  extent,  in  most  pathological  conditions  of  the 
pancreas  may  be  classified  as  follows:  (i)  physical  signs, 
(2)  digestive  symptoms,  (3)  metabolic  symptoms,  (4) 
symptoms  produced  by  artificial  means. 

I.  Physical  Signs. — (a)  Tumour. — The  situation  of  the 
pancreas,  behind  the  stomach  and  in  front  of  the  spinal 
column,  places  it  in  a  very  unfavourable  position  for 
palpation,  and,  normally,  if  the  patient  be  at  all  stout, 
it  can  only  be  felt  indistinctly;  but  when  the  patient  is 
thin,  and  especially  in  cases  of  gastroptosis,  it  can  be 
readily  defined,  if  the  muscles  are  relaxed  and  a  warm  flat 
hand  is  applied  firmly  to  the  epigastric  region.  It  is 
commonly  stated  in  text-books  that  acute  and  chronic 
inflammation,  and  even  abscess  of  the  pancreas,  rarely, 


General  Symptomatology  and  Diagnosis         313 

if  ever,  cause  perceptible  enlargement  of  the  organ,  but 
this  is  not  correct,  for  in  many  cases  a  distinct  swelling 
may  be  felt,  which,  in  acute  cases,  is  made  up  of  the 
enlarged  pancreas,  with  surrounding  effusions  of  blood 
and  inflammatory  fluid  and  matted  omentum ;  in  sub- 
acute cases  the  swelling  is  due  to  suppuration ;  and  in 
chronic  inflammation  it  arises  from  tumefaction  of  the 
gland  itself.  In  cancer  of  the  head  of  the  pancreas  the 
only  tumour  that  is  ordinarily  felt  is  that  due  to  the  en- 
larged gall-bladder,  which  can  be  readily  palpated  in  a 
considerable  proportion  of  cases.  Tumours  of  the  body 
or  tail,  as  well  as  some  growths  of  the  head  of  the  gland, 
can  be  readily  distinguished,  and  by  distending  the  stomach 
with  gas,  either  by  means  of  bicarbonate  of  soda  and 
tartaric  acid  given  in  separate  doses,  or  by  pumping  in  air 
through  the  stomach-tube,  the  relation  of  the  stomach  to 
the  tumour  can  be  satisfactorily  made  out.  Resonance 
on  percussion,  owing  to  the  position  of  the  stomach,  unless 
this  organ  is  empty,  communicated  non-expansile  pulsa- 
tion, and  very  slight  movement  on  deep  inspiration  are 
characteristic  of  swellings  of  the  pancreas.  In  cystic 
diseases  of  the  gland  a  tumour  is  frequently,  at  first,  the 
only  symptom ;  the  position  and  relation  of  such  a  tumour 
depend  on  the  part  of  the  organ  from  which  it  springs, 
as  we  shall  show  later.  It  will  thus  be  seen  that  the 
absence  of  a  tumour  does  not  negative  serious  disease  of 
the  pancreas,  but  the  presence  of  a  swelling,  when  taken 
with  other  symptoms,  affords  valuable  evidence  in  favour 
of  a  pancreatic  lesion. 

(6)  Fever. — A  rise  of  temperature  is,  as  a  rule,  associated 
with  acute  and  subacute  pancreatitis,  but  only  rarely 
with  any  of  the  more  chronic  forms  of  inflammation. 
Cystic  disease,  calculus,  and  new-growth  do  not  generally 
give  rise  to  fever.  In  acute  pancreatitis  the  temperature 
may  be  high,  but  in  some  cases,  as  in  the  hasmorrhagic 
form,    it  .  is    usually   subnormal.     The   temperature   in 


314       The  Pancreas:  Its  Surgery  and  Pathology 

suppurative  pancreatitis  is  generally  irregular,  and  may 
assume  a  hectic  type,  but  occasionally  it  is  subnormal. 
A  persistent  temperature  of  ioi°F.  to  102°  or  io3°F., 
associated  with  rigors,  was  observed  by  one  of  us  in  a  case 
of  pancreatitis  with  abscess  formation.  In  cancer  of 
the  head  of  the  pancreas  the  temperature  is  generally 
subnormal,  although  occasionally  there  may  be  fever 
from  attendant  complications,  such  as  cholangitis  and 
abscess  of  the  liver.  It  will  thus  be  seen  that  fever  as  a 
symptom  of  disease  of  the  pancreas  is  extremely  variable, 
and,  alone,  is  no  guide,  though  when  associated  with 
digestive,  metabolic,  and  other  signs,  it  may  be  of  con- 
siderable assistance  in  making  a  differential  diagnosis. 

(c)  Pain  and  Tenderness. — These  symptoms,  although 
important  when  present,  are  so  variable  that  even  their 
complete  absence  is  no  proof  that  the  pancreas  is  normal. 
Both  pain  and  tenderness  are,  as  a  rule,  absent  in  malig- 
nant disease  of  the  head  of  the  pancreas,  but  in  exceptional 
cases  of  carcinoma  and  sarcoma  of  the  head,  body,  or 
tail  the  pain  may  be  excruciating.  This  is  due  either  to 
pressure  on,  or  involvement  of,  the  great  sympathetic 
ganglia,  or  to  pressure  on,  or  invasion  of,  neighbouring 
viscera,  particularly  the  stomach  and  duodenum.  Small 
scirrhus  tumours  are,  as  a  rule,  characterised  by  absence 
of  pain,  while  large  growths  are  often  marked  by  constant 
and  extreme  agony.  In  the  various  forms  of  pancreatitis 
pain  and  tenderness  in  the  epigastrium  are  generally  well 
marked.  The  more  acute  inflammations  are  characterised 
by  excessive  tenderness  on  pressure,  the  presence  of  a 
tender  spot  just  above  and  to  the  right  of  the  umbilicus, 
rigidity  of  the  recti,  and  pain  of  an  agonising  character. 
The  pain  in  hsemorrhage  into  the  pancreas  is  intermittent, 
being  at  times  severe  and  of  a  colicky  character,  then 
diminishing  or  disappearing,  to  return  later  with  increased 
intensity.  In  chronic  pancreatitis  pain  and  tenderness, 
although  usually  present,  may  be  but  little  marked.     In 


General  Symptomatology  and  Diagnosis         315 


some  cases,  however,  the  pain  is  paroxysmal  and  severe, 
and  epigastric  tenderness  is  pronounced.  Cysts  are 
frequently  painless  and  free  from  tenderness,  but  in  some 
instances  both  pain  and  tenderness  are  well  marked. 
Even  in  abscess  of  the  pancreas  pain  is  not  a  constant 
symptom.  It  may  be  absent,  as  in  the  case  reported  by 
Stibler,  but  in  the  majority  of  cases  both  pain  and  tender- 
ness are  pronounced.  Calculus  of  the  pancreas  may  exist 
for  years  undetected,  and 
unsuspected,  without  caus- 
ing any  pain.  If,  however, 
the  calculus  reaches  the  ori- 
fice of  the  pancreatic  duct, 
or  is  impacted  in  the  ampulla 
of  Vater,  severe  paroxysmal 
pain,  resembling  a  gall-stone 
seizure,  will  occur  and  be  as- 
sociated with  jaundice.  As 
to  the  character  of  the  pain, 
it  may  be  continuous  or 
paroxysmal,  and  may  be 
limited  to  the  epigastrium 
or  radiate  around  either  side 
of  the  thorax.  Pain  in  the 
back,  under  the  left  scapula, 
or  between  the  scapulae,  is 
more  frequent  than  pain  be- 
neath the  right  scapula  in  pancreatic  disease,  thus  serving 
to  distinguish  it  from  gall-bladder  pain.  "  Coeliac  neural- 
gia" was  a  term  long  ago  applied  to  epigastric  pain  such 
as  is  associated  with  some  forms  of  pancreatic  disease,  and 
such  pain  may  radiate  to  the  cardiac  region  and  resemble 
angina  pectoris,  both  in  its  intensity  and  in  its  effect  upon 
the  circulation.  It  will  thus  be  seen  that,  while  pain  is  a 
guide  to  diagnosis,  it  is  not  pathognomonic  of  any  special 
form  of  pancreatic  disturbance,  except  acute  pancreatitis. 


Fig.  113. — Most  frequent 
site  of  the  tender  spot  in  inflam- 
matory affections  of  the  pan- 
creas. 


3i6       The  Pancreas:  Its  Surgery  and  Pathology 

{d)  Pressure  Symptoms. — Owing  to  involvement  of  the 
portal  vein,  ascites  is  seen  at  times  in  the  later  stages 
of  cancer  of  the  pancreas,  and,  when  there  is  also  pressure 
on  the  inferior  vena  cava,  oedema  of  the  lower  limbs  will 
occur.  Pressure  on  the  portal  vein  may  also  cause  en- 
largement of  the  spleen,  and  give  rise  to  hemorrhoids. 
In  those  rare  cases  where  the  duodenum  is  surrounded  by, 
or  partly  surrounded  by,  the  head  of  the  pancreas,  malig- 
nant disease,  or  even  inflammation  of  the  head  of  the 
gland,  may  lead  to  obstruction  of  the  passage  of  the 
stomach  contents,  causing  gastric  dilatation  and  vomiting, 
as  in  pyloric  stenosis. 

The  stomach,  duodenum,  and  colon  may  also  be  pressed 
upon  by  cysts  or  new-growths  of  the  pancreas,  and  be 
seriously  displaced;  the  stomach,  for  instance,  may  be 
pushed  upwards  beneath  the  diaphragm  or  downwards 
below  the  umbilicus.  Distension  of  the  gall-bladder, 
with  jaundice,  is  so  frequently  found  in  cancer  of  the  head 
of  the  pancreas  that  it  is  now  a  well-recognised  sign  of 
the  disease,  but  it  must  be  remembered  that  in  some  cases 
of  chronic  pancreatitis  a  similar  sequence  of  events  may 
occur,  the  presence  or  absence  of  the  sign  in  this  instance 
being  determined  by  the  relation  of  the  common  duct  to 
the  head  of  the  pancreas.  In  some  cases  the  hepatic  duct 
may  be  pressed  upon  when  the  common  duct  is  free,  as  in 
a  case  coming  under  our  observation,  where,  owing  to  a 
prolongation  upwards  of  the  pancreas  being  involved  in  a 
chronic  inflammation  of  the  gland,  there  was  jaundice 
without  distension  of  the  gall-bladder.  The  pressure  of  a 
pancreatic  cyst  upwards,  on  to  the  under  surface  of  the 
diaphragm,  may  cause  dyspnoea,  from  interference  with 
the  functions  of  the  heart  or  lungs,  and,  in  cases  of  inflam- 
matory effusion  into  the  lesser  peritoneal  sac,  there  may 
be  pressure  on  the  pericardium,  through  the  diaphragm, 
leading  to  distressing  cardiac  symptoms.  Occasionally 
hydronephrosis  may  be  produced  by  the  pressure  of  pan- 


General  Symptomatology  and  Diagnosis         317 

creatic  tumours  on  one  or  other  ureter,  and  pressure  on, 
or  involvement  of,  the  solar  plexus  may  give  rise  to  agon- 
ising pain. 

(e)  HoBmorrhage. — In  inflammatory  disease  and  malig- 
nant growths  of  the  pancreas  there  is  a  well-marked 
hsemorrhagic  tendency,  which  is  not  only  seen  at  opera- 
tion, but,  in  advanced  cases,  may  be  manifest  by  bleeding 
from  mucous  surfaces  and  by  haemorrhages  into  the  skin 
or  subcutaneous  tissues,  so  that  the  patient  bruises  very 
readily.  Profuse  and  uncontrollable  haemorrhage  from 
the  mucous  surfaces  was  the  cause  of  death  in  the  case  of 
pancreatitis  above  referred  to,  where  there  was  a  pro- 
longation of  the  head  of  the  pancreas  upwards  on  to  the 
hepatic  duct,  and  in  several  cases  of  cancer  of  the  pan- 
creas operated  on  by  one  of  us,  bleeding  has  cost  the 
patient  his  life.  For  instance,  this  occurred  in  a  case 
sent  by  Professor  Clifford  Albutt,  which  was  operated 
on  in  1888.  Cholecystotomy  was  followed  by  persistent 
oozing  of  the  blood  from  the  interior  of  the  gall-bladder, 
and  from  the  stitch  punctures,  which  resisted  all  the  then 
known  remedial  measures,  and  proved  fatal  on  the  ninth 
day.  In  another  case  of  cancer  of  the  head  of  the  pan- 
creas, sent  by  Dr.  W.  Scatterty,  of  Keighley,  a  cerebral, 
haemorrhage  on  the  tenth  day  produced  a  fatal  result. 
In  neither  of  the  cases  was  there  any  peritonitis,  or  other 
cause  than  the  haemorrhage,  to  account  for  death.  That 
the  hsemorrhage  in  these  cases  is  not  entirely  dependent 
upon  the  jaundice,  but  is  associated  with  the  changes 
induced  in  the  blood  by  the  pancreatic  lesion,  is  shown 
by  the  fact  that  patients  with  equally  profound  jaundice, 
but  in  whom  there  is  no  disease  of  the  pancreas,  do  not 
bleed  to  anything  like  the  same  extent.  Thus,  in  a  patient 
seen  with  Dr.  T.  Churton  in  1889,  the  jaundice  wasiquite 
as  deep  as  in  either  of  those  just  quoted,  but  there  was  no 
haemorrhage,  although  the  man  lived  several  weeks,  and 
ultimately  died  from  suppurative  cholangitis  and  exhaus- 


3i8       The  Pancreas:  Its  Surgery  and  Pathology 

tion,  for  the  obstruction  was  dependent  on  cancer  of  the 
common  bile-duct  above  the  entrance  of  the  pancreatic 
duct.  The  tendency  to  haemorrhage,  both  at  operation 
and  after,  can  be  successfully  counteracted  by  the  admin- 
istration of  calcium  chloride,  in  30-grain  doses,  thrice 
daily,  for  from  twenty-four  to  forty-eight  hours  before 
operation,  and  by  enema,  in  30-grain  doses,  twice  daily 
for  forty-eight  hours  afterwards.  The  following  cases 
illustrate  the  efficiency  of  this  procedure  subsequent  to 
operation,  and  the  danger  that  may  arise  from  its  absence 
or  too  early  disuse : 

A  woman,  aged  thirty-eight  years,  was  suffering  from 
deep  jaundice,  associated  with  gall-stones  in  the  common 
duct  and  chronic  pancreatitis.  There  was  no  bleeding 
at  the  time  of  the  performance  of  duodeno-choledocho- 
tomy,  as  calcium  chloride  had  been  administered  for 
several  days  before  operation.  The  drug  was  inadver- 
tently omitted  after  operation,  and  on  the  third  day 
violent  haemorrhage  occurred,  which  was  arrested  by 
opening  up  the  wound  and  packing  with  gauze,  and  at 
the  same  time  giving  calcium  chloride  in  60-grain  doses 
twice,  and  afterwards  in  30-grain  doses  for  several  days. 
No  recurrence  of  bleeding  occurred  and  a  good  recovery 
was  made. 

In  the  case  of  a  male  patient,  aged  forty-two  years, 
suffering  from  cirrhosis  of  the  liver,  gall-stones  in  the 
common  duct,  and  chronic  pancreatitis,  no  bleeding 
occurred  at  operation,  owing  to  the  previous  administra- 
tion of  lime  salts.  In  consequence  of  the  absence  of  haem- 
orrhage the  calcium  chloride  was  left  off  the  second  day 
after  operation.  Bleeding  occurred  very  freely  on  the 
sixth  day,  in  the  form  of  general  oozing,  which  was  per- 
manently arrested  by  the  free  administration  of  calcium 
chloride,  after  which  recovery  occurred. 

In  a  case  of  suppurative  catarrh  of  the  pancreas  in  a 
gentleman,  aged  sixty-five  years,  the  same  freedom  from 
haemorrhage  was  found  at  operation,  after  the  administra- 
tion, for  some  days,  of  calcium  chloride,  which  was  not 
continued,  as  the  rectum  was  intolerant  of  injections. 
On  the  seventh  day  free  bleeding  occurred,  which  was 


General  Symptomatology  and  Diagnosis        319 

arrested  by  giving  thirty  grains  of  calcium  chloride  every 

two  hours  by  the  mouth. 


(/)  Jaundice. — The  now  well-recognised  relation  be- 
tween gall-stone  trouble  and  pancreatic  disease  would 
lead  one  to  expect  that  jaundice  would  be  a  frequent 
accompaniment  of  diseases  of  the  pancreas,  but  the  symp- 
tom is  by  no  means  constant.  The  relation  of  the  com- 
mon bile-duct  to  the  duct  of  Wirsung,  and  to  the  head  of 
the  pancreas,  is  generally  the  determining  factor.  If, 
as  is  the  case  in  38  per  cent,  of  bodies  (Hellyj,  the  common 
duct  passes  behind  the  head  of  the  pancreas,  either  an 
acute  or  a  chronic  pancreatitis,  or  even  a  cancer  of  the 
pancreas,  may  run  its  course  without  the  appearance  of 
jaundice;  but  if  the  common  duct  lies  in  a  deep  groove, 
or  is  embedded  in  the  head  of  the  gland,  as  occurs  in 
62  per  cent,  of  cases,  either  pancreatitis  or  growi;h  of  the 
head  of  the  organ  must  necessarily  compress  the  bile-duct 
and  lead  to  jaundice  of  greater  or  less  intensity.  It  may 
perhaps  be  only  a  coincidence,  but  it  is  noteworthy  that 
in  62  per  cent,  of  our  cases  of  chronic  pancreatitis  asso- 
ciated with  cholelithiasis  bile-pigments  were  found  in  the 
urine  before  operation,  and  in  38  per  cent,  there  w^as 
neither  jaundice  nor  bile-pigment  in  the  luine.  Chronic 
pancreatitis,  not  associated  with  the  presence  of  gall- 
stones in  the  common  duct,  was  accompanied  by  jaundice 
in  16  per  cent,  of  our  cases,  the  icterus  in  these  instances 
being  probably  due  either  to  compression  of  the  common 
duct  by  the  swollen  head  of  the  pancreas,  or  to  an  ascend- 
ing catarrh  from  the  duodenum,  which  simultaneously 
involved  the  pancreatic  and  biliary  passages.  In  pan- 
creatic calculus  jaundice  may  occur  if  the  stone  lodges  in 
the  ampulla  of  Vater.  Acute  hasmorrhagic  pancreatitis 
may  be  accompanied  by  slight  jaundice,  especially  when 
it  results  from  the  impaction  of  a  small  gall-stone  in  the 
duodenal  outlet  of  the  ampulla  of  Vater. 


320       The  Pancreas:  Its  Surgery  and  Pathology 

Deep  jaundice,  with  a  distended  gall-bladder,  is  signifi- 
cant of  cancer  of  the  head  of  the  pancreas,  whereas  if 
the  cause  of  the  jaundice  be  gall-stones  in  the  common 
duct  the  gall-bladder  is  nearly  always  contracted  and 
cannot  be  felt.  The  jaundice  met  with  in  cancer  develops 
without  pain,  slowly  and  insidiously,  but  steadily.  As  the 
cachexia  increases  the  patient's  skin  assumes  a  ghastly 
slaty  appearance  in  many  instances,  so  that  instead  of  the 
saffron  yellow  colour  of  cholelithiasis  there  is  seen  the 
so-called  "black  jaundice." 

(g)  Emaciation. — Ever  since  pancreatic  disease  has  been 
recognised,  emaciation  has  been  regarded  as  a  striking 
symptom.  In  some  cases  of  chronic  inflammation  there 
is  a  very  marked  loss  of  flesh,  which  is  rapidly  regained 
after  a  cure  of  the  condition  has  been  effected  by  opera- 
tion. Thus,  a  patient  who  was  operated  on  by  one  of  us 
for  the  removal  of  a  calculus  obstructing  the  pancreatic 
duct  had  lost  eight  stones  in  a  little  over  two  years,  but 
rapidly  regained  his  normal  weight  after  the  operation. 
In  another,  and  similar  case,  the  patient  had  lost  flve 
stones  in  three  months,  but  gained  three  stones  in  the 
same  period  after  his  condition  had  been  relieved  by  opera- 
tion. It  is  not  surprising  that  emaciation  should  occur 
in  cancer  of  the  pancreas,  in  which,  indeed,  it  is  most 
marked,  or  in  diabetes  of  pancreatic  origin,  but  it  may 
also  be  met  with  in  cystic  disease,  as  in  Kuster's  case,  in 
which  the  patient  lost  two  stones  five  pounds  in  four 
months,  and  it  is  also  seen  in  calculus  disease.  The  dis- 
turbance of  digestion  may  afford  a  sufficient  explanation 
in  some  cases,  but  in  malignant  disease  and  cases  of 
atrophy  of  the  gland,  interference  with  the  metabolic 
functions  of  the  pancreas  are  probably,  in  part,  respon- 
sible for  the  rapid  wasting  that  is  met  with  in  these  con- 
ditions. 

2.  Digestive  Symptoms. — (a)  Dyspepsia  and  Alteration 
of  A p petite. —Dys-pe-ptic  disturbances  are  very  constantly 


General  Symptomatology  and  Diagnosis        321 

associated  with  affections  of  the  pancreas.  They  take 
the  form  of  anorexia,  pain,  and  fulness  after  food,  flatu- 
lence with  offensive  eructations,  heart-burn,  nausea,  dis- 
taste for  fats  and  for  meat.  In  the  case  of  a  woman 
aged  twenty-eight,  to  be  referred  to  later  under  "  Chronic 
Pancreatitis,"  where  a  biliary  fistula  was  established  in 
order  to  relieve  the  jaundice  and  by  drainage  to  cure  the 
pancreatitis  that  was  causing  pressure  on  the  common 
bile-duct,  all  the  above  symptoms  were  well  marked, 
both  before  the  operation  and  when  the  fistula  was  dis- 
charging, and  the  patient  had  such  a  loathing  for  food 
that  she  became  greatly  emaciated.  Within  twelve  hours 
of  a  cholecystenterostomy  being  performed,  by  which 
the  pancreatic  juice  and  bile  were  diverted  into  the  duo- 
denum, she  expressed  herself  as  hungry,  a  sensation 
she  said  she  had  not  felt  for  many  months.  During  the 
month  succeeding  the  operation  she  put  on  flesh  rapidly, 
and  three  months  later  had  gained  two  stones  in  weight. 
In  several  cases  where  dyspeptic  symptoms  have  been 
pronounced,  both  in  simple  and  malignant  disease  of  the 
pancreas,  the  administration  of  pancreatic  preparations 
after  meals  has  been  found  to  give  marked  relief,  and  the 
patients  have  gained  in  weight. 

(6)  Nausea  and  Vomiting. — These  symptoms  are  fre- 
quently associated  with  acute  pancreatitis,  and,  in  some 
instances,  the  vomiting  may  be  so  violent  as  to  suggest 
intestinal  obstruction.  In  other  forms  of  pancreatic 
disease  vomiting  is  not  a  common  symptom,  and,  when 
present,  is  often  due  to  neighbouring  organs — stomach 
or  duodenum— participating  in  the  trouble  or  being 
pressed  upon.  There  is  nothing  specially  characteristic 
in  the  vomited  matter,  unless,  as  rarely  occurs,  extremely 
offensive  pus  and  altered  blood  are  brought  up,  as  in 
cases  where  a  pancreatic  abscess  has  ruptured  into  the 
stomach.  In  one  of  our  cases  of  erosion  of  the  pancreas 
by  chronic  gastric  ulcer  the  pus  vomited  was  so  offen- 


322       The  Pancreas:  Its  Surgery  and  Pathology 

sive  that  the  nurses  in  attendance  were  made  sick  by  the 
odour.  The  case  was  treated  successfully  by  gastro- 
jejunostomy. In  acute  pancreatitis  altered  blood,  the 
so-called  "black  vomit,"  is  seen  at  an  earlier  stage  than 
in  any  other  peritoneal  condition. 

(c)  Fceces. — The  condition  of  the  fseces  furnishes,  in 
many  instances,  what  might  almost  be  termed  a  charac- 
teristic sign  of  pancreatic  disease.  In  these  cases  the 
motions  are  exceedingly  bulky,  soft,  greasy,  and  pale. 
They  contain  undigested  fat  and  muscle  fibre,  and  are 
extremely  offensive.  Patients  frequently  state  that  they 
suffer  from  diarrhoea,  but  investigation  will  show  that 
this  is  hardly  correct,  for,  although  the  stools  are  bulky 
and  soft,  they  are  not  liquid  in  consistency.  The  symp- 
tom is  a  very  noticeable  one,  and,  when  it  occurs  in  cases 
of  jaundice,  may  nearly  always  be  taken  as  indicating 
that  the  pancreatic  functions  are  being  interfered  with, 
either  by  an  interstitial  pancreatitis  or  some  other  form 
of  pancreatic  disease.  It  is  more  common  in  inflamma- 
tory conditions  than  in  cancer,  probably  because  the 
appetite  is  more  interfered  with  by  the  latter  than  the 
former,  so  that  in  pancreatitis  the  full  effects  of  the  lack 
of  digestive  powers  are  seen.  For  the  same  reason  the 
symptom  is  more  apt  to  be  noticed  in  the  earlier  than 
in  the  later  stages  of  pancreatic  affections,  unless  large 
amounts  of  milk  are  being  given,  when  the  bulk  of  it  may 
pass  away  in  the  form  of  spurious  diarrhoea.  In  some 
cases  there  is  constipation,  the  motions  being  still  very 
bulky,  however,  and,  as  a  rule,  pale. 

The  bulk  of  these  motions,  out  of  all  proportion  to  the 
amount  of  food  taken,  is  to  be  attributed  partly  to  the 
abnormal  quantity  of  undigested  food  materials  that 
they  contain,  and  partly  to  the  excessive  fermentation 
that  takes  place  in  the  intestines.  Their  frequency  is 
due  to  their  bulk,  but  is  no  doubt  contributed  to  by  the 
excess  of  irritating  by-products  they  contain.     The  ques- 


General  Symptomatology  and  Diagnosis         323 

tion  of  their  lack  of  colour  has  already  been  discussed 
(page  225),  but  it  may  be  repeated  that  it  does  not  neces- 
sarily arise  from  the  absence  of  bile,  as  precisely  similar 
stools  may  be  seen  in  cases  of  pancreatic  disease  when 
there  is  obstruction  of  the  biliary  passages,  and  when  there 
is  no  obstruction  whatever  to  the  free  flow  of  bile  into 
the  intestine. 


Fig.  114. — Microscopical  characters  of  the  residues  met  with  in  the 
stools  in  case  of  pancreatic  disease  and  biliary  obstruction:  a,  Striated 
muscle  fibres;  5,  fat  globules;  c,  free  fatty  acid  crystals;  d,  combined 
fatty  acid  (soap)  crystals. 


Steatorrhcea  or  fatty  stools  have  long  been  recognised 
as  a  symptom  of  disease  of  the  pancreas.  Kuntzmann, 
in  1820,  described  the  case  of  a  man  who  died  from  chronic 
induration  of  the  pancreas,  with  complete  obliteration  of 
the  common  bile-duct  and  pancreatic  duct,  where  large 
stools  containing  undigested  fat  were  seen.  In  his  record 
of  seven  cases  of  disease  of  the  pancreas,  Bright,  in  1833, 
noted  an  excess  of  fat  in  the  faeces  of  three.     Fles,  in  1864, 


324       The  Pancreas:  Its  Surgery  and  Pathology 

reported  the  case  of  a  diabetic,  who  had  eaten  much 
bacon  and  fat  meat,  with  stools  containing  such  a  quan- 
tity of  fat  that  it  could  be  skimmed  off  the  surface  by 
the  ounce.  The  fat  disappeared  when  an  emulsion  of 
calf  pancreas  was  administered,  but  reappeared  as  soon 
as  the  emulsion  was  omitted.  The  patient  died  of  phthi- 
sis, and  post-mortem  the  pancreas  was  found  to  be  re- 
placed by  fibrous  tissue,  with  scarcely  any  recognisable 
trace  of  gland  substance  left.  In  many  of  the  earlier 
recorded  cases  of  steatorrhoea  the  pancreatic  disease  was 
associated  with  jaundice,  and  there  was  some  doubt  as  to 
the  part  the  lack  of  bile  played  in  producing  the  condi- 
tion. More  recent  observations  have  shown,  however,  that 
fatty  stools  occur  in  diseases  of  the  pancreas  independently 
of  jaundice,  and  that  in  such  cases  the  steatorrhoea  is 
to  be  attributed  directly  to  the  pancreatic  lesion.  Fitz, 
of  Boston,  in  an  address  before  the  Congress  of  American 
Physicians  and  Surgeons  in  May,  1903,  gave  in  tabular 
form  the  relationship  between  visible  faecal  fat,  jaundice, 
diabetes,  and  pancreatic  disease  in  twenty-nine  cases 
collected  from  the  literature  of  the  subject.  He  found 
that  in  about  three-fifths  the  steatorrhoea  was  attributable 
to  disease  of  the  pancreas  unassociated  with  either 
jaundice  or  diabetes,  that  in  two-fifths  there  was  pan- 
creatic disease  with  either  jaundice  or  diabetes  in  about 
equal  proportions,  and  that  in  a  few  instances  there  was 
a  combination  of  pancreatic  disease,  diabetes,  and  jaun- 
dice. 

In  the  following  case,  reported  by  Oser,  the  appearance 
of  steatorrhoea  in  pancreatic  disease,  before  the  onset  of 
jaundice,  is  well  shown: 

A  woman,  aged  thirty-nine  years,  had  had  diarrhoea 
since  the  summer  of  1892.  The  patient  became  emaci- 
ated, yet  the  appetite  remained  good.  Faecal  evacuations 
appeared  regularly  every  night,  were  unusually  copious, 
of  the  consistency  of  thick  porridge,  and  of  cadaverous 


General  Symptomatology  and  Diagnosis        325 

odour,  chocolate-coloured,  and  always  abundantly  cov- 
ered with  fat  rings.  On  January  11,  1893,  he  saw  the 
patient  for  the  first  time  and  found  steatorrhoea.  The 
investigations  of  the  stools  gave  the  following  results: 
"  Large  in  amount  and  of  the  consistency  of  thick  porridge ; 
in  the  sediment  were  scattered  white  particles.  Micro- 
scopic examination  showed:  (i)  very  numerous  frag- 
ments of  striated  muscle  in  the  main  with  well-preser\-ed 
structure;  (2)  numerous  fat  acid  needles  and  fat  drops; 
and  (3)  bacteria  and  detritus.  After  drying  the  stools 
for  several  days  on  the  water-bath  in  order  to  determine 
the  amount  of  fat,  there  were  obtained  4.6325  grams  of 
solid  substance,  in  which  2.1265  grams  were  fat,  repre- 
senting 45.8  per  cent,  of  the  dried  residue.  The  other 
extract  consisted  almost  entirely  of  neutral  fat."  On 
January  i8th  he  found  in  the  epigastrium  a  distinct,  hard, 
round  tumour,  w^hich  was  diagnosed  as  carcinoma  of  the 
head  of  the  pancreas.  In  March  jaundice  developed. 
At  the  beginning  of  April  an  exploratory  laparotomy  was 
undertaken  and  the  diagnosis  confirmed. 

Fatty  stools  have  been  most  frequently  described  in 
connection  with  cancer  of  the  pancreas,  but  they  have 
also  been  met  with  in  fibro-adenoma  (Biondi),  calculi 
(Gould,  Chari,  Reeves,  Cowley,  Capparelli,  etc.),  cysts 
(Gould,  Goodman,  Bull,  etc.),  syphilitic  atrophy  (Demme), 
fibrosis  (Kuntzmann) ,  fatty  degeneration  (Reeves,  Motta) , 
abscess  (Harley),  and  diabetes  (Silver,  Le  Nobel,  Hirsch- 
feld,  etc.).  In  most  instances  reliance  has  been  placed 
upon  naked-eye  observations,  and  in  only  a  few  have 
actual  determinations  of  the  amount  of  fat  present  been 
made.  Ziehl  states  that,  in  a  case  of  cancer  of  the  pan- 
creas with  jaundice  that  he  investigated,  the  fat  formed 
about  50  per  cent,  of  the  dry  weight  of  the  faeces,  and 
Demme  found  from  64  to  73  per  cent,  of  fat  in  the  asbes- 
tos-like fasces  of  a  case  of  congenital  syphilis,  with  atrophy 
of  the  pancreas,  that  he  examined. 

In  some  cases,  where  fat  is  parted  with  in  abundance,  the 
greasy  bulky  motions,  occasionally  coated  with  oil  which 


326       The  Pancreas:  Its  Surgery  and  Pathology 

may  float  on  the  surface  of  the  urine  passed  at  the  same 
time,  are  sufficiently  striking  to  attact  the  attention  of  the 
patient  himself,  but  in  others,  although  a  large  amount  of 
fat  may  be  passed,  it  can  only  be  recognised  on  chemical 
examination,  as  our  own  experience  has  frequently  dem- 
onstrated. It  is  therefore  essential,  if  full  advantage  is  to 
be  taken  of  the  occurrence  of  steatorrhoea  as  a  symptom  of 
disease  of  the  pancreas,  that  the  stools  should  be  submitted 
to  careful  quantitative  analysis.  The  method  we  have 
described  in  a  previous  chapter  gives  satisfactory  results 
for  clinical  purposes,  and  has  the  advantage  of  occupying 
much  less  time  than  the  processes  usually  adopted; 
further,  it  has  the  additional  advantage  of  giving  not  only 
the  amount  of  unabsorbed  fat  present  in  the  stools,  but 
of, supplying  information  as  to  quantities  of  saponified 
and  unsaponified  fat  that  the  motion  contains,  with  but 
little  extra  trouble. 

We  have  now  employed  this  method  of  investigation 
in  a  large  number  of  cases,  and  found  that  in  many  it 
has  given  results  of  the  greatest  value  in  diagnosis.  As 
a  rule,  it  has  been  found  that  when  the  functions  of 
the  pancreas  have  been  seriously  interfered  with  there 
has  not  only  been  an  excess  of  "total  fat,"  but  that  the 
relation  between  the  "neutral  fats"  and  combined  "fatty 
acids"  has  been  disturbed,  the  former  being  in  excess, 
whereas  in  cases  of  simple  jaundice  or  biliary  obstruction, 
although  the  amount  of  "  neutral  fat"  may  also  have  been 
abnormal,  the  combined  "fatty  acids"  formed  the  larger 
proportion  of  the  fat  in  the  dry  faeces.  In  some  cases  of 
malignant  disease  of  the  pancreas  as  much  as  93  per  cent, 
of  the  dry  weight  of  the  fasces  has  been  found  to  be  fat, 
and  even  in  chronic  pancreatitis  we  have  found  from  80 
to  82  per  cent.  The  average  amount  in  malignant  disease, 
however,  has  been  77  per  cent.  In  chronic  pancreatitis 
more  than  60  per  cent,  has  been  uncommon,  and  in  some 
instances  an  amount  within  the  limits  for  a  normal  mixed 


General  Symptomatology  and  Diagnosis        327 

diet  has  been  met  with.  The  "neutral  fats"  in  cancer 
of  the  pancreas  have  ranged  from  69  per  cent,  to  31  per 
cent.,  and  the  combined  "fatty  acids"  from  36  per  cent, 
to  3  per  cent.,  with  an  average  for  the  former  of  50  per 
cent.,  and  for  the  latter  of  27  per  cent.  The  "neutral 
fats"  and  combined  "fatty  acids"  are  normally  present 
in  equal  proportions,  but  in  chronic  pancreatitis  an  aver- 
age of  32  per  cent,  of  the  one  and  18  per  cent,  of  the  other 
has  been  obtained.  In  our  cases  of  biliary  obstruction 
not  associated  with  pancreatitis,  on  the  other  hand,  the 
average  amount  of  "neutral  fat"  has  been  18  per  cent., 
and  of  combined  "fatty  acid"  23  per  cent.,  the  "total 
fat"  being  42  per  cent. 

In  some  cases  of  undoubted  pancreatic  disease,  how- 
ever, we  have  found  that  there  was  no  excess  of  fat  in 
the  stools,  and  that  even  where  an  excess  was  present 
the  relation  between  the  "neutral  fats"  and  combined 
"fatty  acids"  was  not  markedly  disturbed,  or  else  that 
there  was  a  more  or  less  marked  excess  of  combined  "  fatty 
acid, ' '  contrary  to  what  might  have  been  expected.  These 
variations  have  usually  been  met  with  in  cases  of  pan- 
creatitis, and  generally  in  the  earlier  stages  of  the  disease. 
The  absence  of  an  excess  of  fat  in  these  cases  is  to  be 
explained  (i)  by  the  food  containing  an  abnormally  small 
proportion  of  fatty  material  owing  to  the  distaste  of  the 
patient  for  fat ;  (2)  by  the  fat  being  of  a  readily  digested 
and  easily  absorbed  kind  {e.g.,  milk,  etc.);  and  (3)  by 
the  action  of  the  fat-splitting  ferment  of  the  stomach. 
The  relatively  high  proportion  of  combined  "fatty  acids" 
may  be  accounted  for  (i)  by  the  action  of  fat-splitting 
bacteria  in  the  intestines;  (2)  by  the  examination  being 
made  at  a  comparatively  early  stage  in  the  disease,  when 
the  flow  of  pancreatic  juice  is  not  diminished,  or  may  be 
actually  increased;  and  (3)  by  an  associated  enteritis 
hurrying  the  contents  of  the  intestine  onwards  to  the  large 
bowel  before  they  have  had  time  to  be  completely  ab- 
sorbed. 


328       The  Pancreas:  Its  Surgery  and  Pathology 

Microscopical  examination  of  the  iseces  may  sometimes 
be  of  assistance  when  a  chemical  examination,  for  various 
reasons,  is  impracticable.  In  serious  pancreatic  disease 
the  stools  show  numerous  fat  globules  and  many  free 
fatty  acid  crystals.  The  latter,  together  with  crystals  of 
combined  fatty  acids,  are  also  seen  in  jaundice,  but  no 
fat  globules  are  usually  met  with  in  this  condition,  unless 
it  is  combined  with  disease  of  the  pancreas.  Microscopi- 
cal examination,  however,  is  only  of  use,  as  a  rule,  in  con- 
firming an  opinion  based  upon  the  naked-eye  characters, 
and  is  far  inferior  as  a  diagnostic  aid  to  a  chemical  investi- 
gation. 

In  interpreting  the  results  of  an  examination  of  the 
fseces  for  undigested  fat  it  has  to  be  borne  in  mind  that, 
in  addition  to  diseases  of  the  pancreas  and  jaundice,  an 
excess  of  fat  may  arise  from  (i)  an  abnormal  quantity 
being  taken  in  the  food,  for  the  capacity  for  digesting  and 
absorbing  fat  is  limited  and  probably  varies  somewhat 
for  different  individuals;  (2)  from  diseases  of  the  intes- 
tines and  mesenteric  glands  that  interfere  with  absorp- 
tion, such  as  sprue,  tuberculosis,  etc. 

If  these  conditions  can  be  excluded  steatorrhoea  is 
suggestive  of  disease  of  the  pancreas,  especially  if  jaun- 
dice is  absent,  and  even  if  there  is  obstruction  of  the 
biliary  passage  an  excess  of  "neutral"  fat  over  combined 
"fatty  acid"  points  to  there  being  some  interference  with 
the  fat-splitting  functions  of  the  pancreas  in  the  majority 
of  cases.  Disappearance  of  the  excess  of  fat  in  the  stools 
on  the  administration  of  preparations  of  pancreas  after 
meals  tends  to  confirm  a  diagnosis  of  pancreatic  mischief. 

The  presence  of  azotorrhoea  as  a  valuable  symptom  in 
diseases  of  the  pancreas  was  first  recognised  by  Fles  in 
1864.  He  found  in  the  stools  of  a  diabetic,  who  was 
proved  post-mortem  to  be  suffering  from  chronic  intersti- 
tial pancreatitis,  large  numbers  of  undigested  muscle  fibres, 
which  disappeared  when  calf's  pancreas  was  administered 


General  Symptomatology  and  Diagnosis        329 

daily,  and  reappeared  when  it  was  omitted.  Le  Nobel 
subsequently  reported  a  similar  case.  Harley  found 
muscle  fibres  in  the  fasces,  in  large  quantities,  in  a  case  of 
pancreatic  abscess,  Kuster  in  a  case  of  pancreatic  cyst, 
Lichtheim  in  a  patient  with  pancreatic  calculi,  and  v. 
Ackeron  and  Oser  have  described  cases  of  cancer  of  the 
pancreas  in  which  the  stools  contained  an  excess  of  striated 
muscle  fibres.  In  twenty  out  of  twenty-four  of  our  cases 
of  cancer  of  the  pancreas,  included  in  the  table  on  page 
214,  numerous  muscle  fibres  were  found  microscopically, 
but  they  were  only  present  in  sixteen  out  of  fifty-six  cases 
of  chronic  pancreatitis.  An  abnormally  large  number 
was  also  observed  in  one  out  of  eight  cases  in  which  there 
was  jaundice  but  no  disease  of  the  pancreas,  and  in  tw^o 
out  of  twelve  cases  in  which  there  was  a  stone  in  the  gall- 
bladder or  common  duct  but  no  pancreatic  disease.  It 
will  thus  be  seen  that  while  an  excess  of  undigested  mus- 
cle fibres  is  frequently  met  with  in  malignant  disease, 
it  is  not  such  a  common  symptom  in  pancreatitis.  It  is 
usually  only  seen  in  advanced  cases  of  cirrhosis,  or  in 
other  lesions  where  a  great  part  of  the  secreting  tissue 
has  been  destroyed,  and  the  formation  of  pancreatic  juice 
is  very  seriously  interfered  with. 

Azotorrhoea  is  not  so  readily  noticed  as  steatorrhoea, 
and  attention  is  hardly  ever  drawn  to  it  by  the  patient. 
In  some  instances  the  undigested  muscle  can  be  recog- 
nised by  the  naked  eye,  but,  in  most,  a  microscopical 
examination  is  necessary.  Microscopical  examination 
is,  however,  likely  to  prove  misleading  unless  a  considera- 
ble number  of  preparations  are  examined  and  muscle 
fibres  are  found  in  all ;  moreover,  it  must  be  remembered 
that  if  much  meat  enters  into  the  diet,  or  there  is  an  enteri- 
tis by  which  the  food  material  is  hurried  through  the  in- 
testine, an  excess  of  muscle  fibres  may  be  met  with  when 
there  is  no  disease  of  the  pancreas.  It  must  also  be  borne 
in  mind  that  gastric  digestion  is  necessary  as  a  prepara- 


330       The  Pancreas:  Its  Surgery  and  Pathology 

tion  for  the  work  of  the  pancreatic  juice  on  meat,  for  if 
the  connective  tissue  binding  the  muscle  bundles  to- 
gether has  not  been  attacked  by  the  gastric  juice,  the 
pancreatic  secretion  can  only  act  from  the  surface,  eating 
its  way  slowly  inwards,  and  consequently  undigested 
muscle  fibre  will  be  passed  in  the  stools. 

As  the  result  of  his  observations  on  the  different  beha- 
viour of  tissue  elements  to  the  gastric  and  pancreatic 
juices,  Schmidt  found  that  the  nuclei  of  cells  were  digested 
by  the  pancreatic  but  not  by  the  gastric  secretion.  He 
therefore  concluded  that  if  undigested  tissue  nuclei  reap- 
pear in  the  faeces  they  afford  evidence  that  the  functions 
of  the  pancreas  are  being  unsatisfactorily  performed, 
and  he  suggested  that,  under  appropriate  conditions,  this 
might  serve  as  a  test  of  pancreatic  efficiency.  Schmidt 
advises  that  small  cubes  of  fresh,  "marbled"  beef,  about 
0.5  to  0.75  cm.  thick,  should  be  hardened  in  alcohol, 
placed  in  little  silk-gauze  bags,  and  preserved  in  alcohol 
until  required.  Before  use  they  are  to  be  well  washed 
in  water  for  several  hours,  placed  in  a  wafer,  and  given 
with  the  food  at  noon  for  several  days.  The  bags  can 
be  easily  recovered  from  the  fseces,  on  rubbing  them 
up  in  water,  and,  after  they  have  been  washed,  the  con- 
tents can  be  examined  fresh,  after  treatment  with  acetic 
acid  or  methylene-blue,  or  they  can  be  hardened,  cut,  and 
stained.  He  states  that  the  nuclei  are  never  preserved  in 
disorders  of  the  liver,  intestine,  or  stomach,  but  that  they 
are  found  intact  in  destructive  lesions  of  the  pancreas, 
and  in  animals  after  the  pancreas  has  been  removed. 

..  The  disadvantages  of  the  method  appear  to  be  that  the 
demonstration  of  the  nuclei  is  not  always  easy,  single  nuclei 
remain  unchanged  in  intense  diarrhoea,  even  when  there 
is  no  disease  of  the  pancreas,  and  the  nuclei  may  disap- 
pear as  the  result  of  putrefactive  changes  in  the  intestine, 
particularly  if  the  material  is  retained  in  the  bowel  more 
than  thirty  hours.     Schmidt  therefore  insists  that  all, 


General  Symptomatology  and  Diagnosis         331 

or  at  least  most,  of  the  nuclei  should  be  preserved  un- 
changed before  it  is  inferred  that  the  pancreas  is  diseased. 
Partial  extirpation  of  the  pancreas  was  found  not  to  pro- 
duce diagnostic  changes,  and  it  is  therefore  improbable 
that  the  method  is  of  great  value  in  any  but  the  most 
advanced  and  serious  pancreatic  lesions. 

The  fasces  are  normally  neutral  or  faintly  alkaline  to 
litmus,  but  in  many  cases  of  pancreatic  disease,  we  have 
found  that  they  were  distinctly  acid.  This  alteration  of 
reaction,  although  by  no  means  constant  or  pathogno- 
monic of  pancreatic  lesions,  may  sometimes  serve  as  a 
confirmatory  sign.  The  specimen  should  be  examined 
as  fresh  as  possible,  and  the  sample  to  be  tested  should 
be  taken  from  the  centre  of  the  faecal  mass,  not  from  the 
surface.  It  can  be  applied  to  moistened  litmus  paper 
on  a  glass  slide,  which  is  then  examined  on  the  reverse 
side,  or  a  fragment  may  be  added  to  a  little  neutral  lit- 
mus contained  in  a  test-tube,  which  is  centrifugalised, 
after  it  has  been  well  shaken. 

One  of  the  most  serious  difficulties  arising  in  connection 
with  the  diagnosis  of  diseases  of  the  pancreas  is  the  differ- 
entiation of  the  jaundice  due  to  cancer  of  the  head  of  the 
gland  from  that  occurring  in  chronic  pancreatitis  and 
common-duct  cholelithiasis.  A  chemical  examination 
of  the  faeces  for  stercohilin  may,  in  many  instances, 
afford  very  considerable  assistance  and  supply  valuable 
confirmatory  evidence.  The  method  of  investigation  we 
have  employed  has  been  described  on  page  213.  Ob- 
struction of  the  common  duct  in  most  cases  of  cancer 
of  the  head  of  the  pancreas,  at  the  time  they  usually- 
come  under  observation,  is,  we  have  found,  generally 
complete,  or  almost  complete,  and  the  fseces  are  therefore 
free  from  stercobilin  or  contain  but  faint  traces.  In 
common-duct  cholelithiasis  and  chronic  pancreatitis, 
on  the  other  hand,  it  has  been  our  experience  that  the 
obstruction  is  rarely  absolute,  so  that  the  faeces  give  a 


332       The  Pancreas:  Its  Surgery  and  Pathology 

distinct,  although  often  subnormal,  reaction  for  sterco- 
bilin.  In  the  table  on  page  214  it  will  be  seen  that 
twenty-two  out  of  twenty-four  cases  of  malignant  disease 
of  the  pancreas  gave  no  stercobilin  reaction,  in  two  traces 
were  found,  and  in  one  only  was  there  a  well-marked 
reaction.  In  eighteen  cases  of  chronic  pancreatitis,  with 
jaundice  and  obstruction  of  the  common  duct,  there  was 
a  well-marked  reaction  for  stercobilin  in  all  but  six,  and 
in  these  six  traces  were  found.  Stercobilin  was  also 
present  in  the  faces  of  eight  cases  of  common-duct  chole- 
lithiasis with  jaundice  but  no  affection  of  the  pancreas, 
in  considerable  amounts  in  five,  and  in  small  quantities 
in  three. 

Blood  may  be  noticed  in  the  motions  occasionally,  but 
it  is  not  a  regular  symptom  until  the  hemorrhagic  ten- 
dency occurs  later  in  the  disease,  or  unless  there  happens 
to  be  a  malignant  growth  ulcerating  into  the  intestine. 
Abscesses  of  the  pancreas  and  pancreatic  cysts  have  been 
known  to  rupture  into  the  bowel  and  their  characteristic 
contents  have  been  found  in  the  motions,  or  even  in  the 
vomited  matter,  as  occurred  in  one  of  our  cases.  A 
necrotic  pancreas  has  been  passed  through  the  intestine, 
and  cases  have  been  reported  by  Leichtenstern  and  Min- 
nich  in  which  pancreatic  calculi  have  been  passed  per 
anum, 

{d)  Sialorrhosa  Pancreatica. — An  increased  flow  of  saliva 
has  been  noted  by  some  observers  in  disease  of  the 
pancreas,  and  particularly  in  cases  of  pancreatic  calculi 
(Holzmann,  Capparelli,  and  Guidiceandra)  and  cysts  of 
the  pancreas  (Battersby  and  Ludolph).  It  has  been  sup- 
posed to  be  due  to  a  reflex  excitation  of  the  salivary 
glands.  The  occasional  association  of  pancreatitis  with 
parotitis  suggests  that  there  is  some  obscure  connection 
between  the  buccal  and  abdominal  "salivary  glands," 
but  excessive  salivation  is  such  a  very  rare  occurrence  in 
pancreatic   disease  that    it    is    possibly  accidental    and 


General  Symptomatology  and  Diagnosis        333 

cannot  be  relied  upon  as  an  aid  to  diagnosis.  We  have 
observed  it  in  two  at  least  of  the  cases  that  have  come 
under  our  notice,  and  have  recently  met  with  a  third  in 
which  it  was  one  of  the  symptoms  that  most  seriously 
troubled  the  patient.  In  this  instance  the  salivation 
ceased  in  a  most  striking  manner  within  forty-eight  hours 
after  he  had  been  operated  on  for  chronic  pancreatitis. 

3.  Metabolic  Symptoms. — (a)  Diabetes  and  Glycosuria. — 
Glycosuria  is  by  no  means  a  common  symptom  of  pan- 
creatic disease,  and  cannot  be  relied  upon  as  a  diagnostic 
symptom.  When  present  it  indicates  a  serious,  although 
not  necessarily  hopeless,  condition.  The  relation  of 
diabetes  to  disease  of  the  pancreas  has  been  discussed  in 
the  chapter  on  diabetes,  and  it  will  be  recollected  that 
both  experimental  and  clinical  observations  have  shown 
that  glycosuria  occurs  only  when  the  greater  part  of  the 
pancreas  has  been  removed  or  destroyed.  The  appear- 
ance of  sugar  in  the  urine,  along  with  other  signs  of  disease 
of  the  pancreas,  therefore  points  to  a  wide-spread  and 
advanced  lesion.  This  is  particularly  the  case  in  chronic 
interstitial  pancreatitis  of  the  interlobular  type,  which  is 
the  form  that  follows  obstruction  of  the  ducts  by  calculi, 
and  is  produced  by  ascending  catarrhal  inflammations 
from  the  duodenum.  Interacinar  pancreatitis  gives  rise 
to  glycosuria  at  an  earlier  stage,  but  appears  to  be  a 
much  less  common  disease  than  the  interlobular  variety. 
Malignant  disease  of  the  pancreas  rarely  gives  rise  to 
diabetes,  and  then  only,  as  a  rule,  when  the  whole  organ 
has  been  destroyed  by  the  growth. 

[b)  Maltosuria  and  Pentosuria. — The  sugar  met  with 
in  diseases  of  the  pancreas  is  usually  dextrose,  but  occa- 
sionally maltose  has  been  found,  and  very  rarely  there 
would  appear  to  be  pentosuria.  Neither  maltosuria 
nor  pentosuria  can  be  regarded  as  pathognomonic  of 
pancreatic  diseases,  and  they  are  of  such  rare  occurrence 
as  to  be  of  no  practical  importance. 


334       The  Pancreas:  Its  Surgery  and  Pathology 

(c)  The  ''Pancreatic''  (Cammidge's)  Reaction  in  the 
Urine.— The  original  method  of  performing  this  reaction, 
as  described  by  one  of  us  in  1904  (see  page  245),  has  to  a 
large  extent  been  superceded  by  the  improved  method 
(page  252).  The  former,  in  our  hands,  had  proved  ex- 
ceedingly useful  in  many  anxious  and  doubtful  cases, 
but,  as  the  interpretation  of  the  results  it  yielded  were 
largely  dependent  upon  the  experience  of  the  observer, 
it  was  difficult  for  those  who  had  not  the  opportunity  of 
frequently  performing  the  test  to  satisfactorily  apply  it 
in  practice.  The  improved  method  has,  we  hope,  over- 
come this  difficulty,  and  also  removed  some  of  the  possible 
sources  of  manipulative  error  in  inexperienced  hands. 

We  have  regularly  employed  the  improved  reaction  since 
the  early  part  of  1905,  and,  as  the  table  on  page  255  shows, 
have  found  that  a  positive  reaction  may  be  expected  in 
all  cases  where  there  are  active  inflammatory  changes 
in  the  pancreas.  Acute  pancreatitis  can  thus  be  distin- 
guished from  intestinal  obstruction,  and  other  conditions 
with  which  it  is  liable  to  be  confused,  and  chronic  pan- 
creatitis, associated  with  obstruction  of  the  common  duct 
by  gall-stones,  or  secondary  to  duodenal  catarrh,  can  be 
differentiated  from  simple  cholelithiasis  and  jaundice, 
etc.,  for  which  a  distinct  method  of  treatment  may  be 
required.  It  is  always  advisable  to  control  the  urine 
examination  by  an  investigation  of  the  fasces,  for  if  the 
results  agree  the  chances  of  a  mistaken  opinion  are  con- 
siderably reduced,  and  are  probably  very  small,  if  the 
analyses  have  been  conducted  by  a  competent  observer. 
A  chemical  examination  of  the  fasces  is  particularly  useful 
in  suspected  cases  of  malignant  disease  of  the  pancreas, 
for,  although  no  reaction  is  obtained  by  the  improved 
method  in  about  75  per  cent,  of  such  cases,  a  crystalline 
deposit,  indicating  an  associated  inflammatory  lesion, 
is  met  with  in  the  remaining  25  per  cent. 

Clinically  it  is  often  a  matter  of  extreme  difficulty  to 


General  Symptomatology  and  Diagnosis        335 

differentiate  chronic  inflammation  of  the  pancreas  from 
cancer,  but  if  the  results  of  a  complete  examination  of 
the  urine  and  faeces,  carefully  and  conscientiously  per- 
formed, are  considered  in  conjunction  with  the  history 
and  symptoms,  the  chance  of  an  erroneous  diagnosis  is 
materially  reduced,  even  in  those  cases  where  the  spread 
of  the  growth  is  giving  rise  to  secondary  inflammatory 
changes  in  the  adjacent  gland  tissue.  In  our  experience 
a  characteristic  "pancreatic"  reaction  in  the  urine  has 
always  been  associated  with  evidence  of  disease  of  the 
pancreas  at  operation,  or  post-mortem,  in  all  cases  where 
it  has  been  possible  to  investigate  the  condition  of  the 
gland,  and  information  kindly  supplied  to  one  of  us  by 
others  regarding  cases  examined  for  them  confirms  our 
opinion  of  the  clinical  value  of  the  test.  Confirmatory 
evidence  is  also  afforded  by  the  way  in  which  the  reaction 
disappears  in  patients  who  have  suffered  from  pancrea- 
titis, after  steps  have  been  taken  to  deal  with  the  condi- 
tion by  operative  means,  and  the  uniform  manner  in 
which  gall-stones  in  a  common  duct  passing  through  the 
head  of  the  pancreas  have  been  associated  with  a  positive 
reaction  in  the  urine,  whereas  when  the  duct  has  passed 
behind  the  pancreas  the  presence  of  calculi  has  not  given 
rise  to  any  reaction.  A  striking  demonstration  of  the 
diagnostic  value  of  the  test  was  afforded  by  a  case  already 
referred  to  in  the  chapter  on  diabetes.  The  urine  from 
this  patient,  who  suffered  from  a  duodenal  growth,  gave 
no  reaction  when  first  examined,  but  later  gave  a  well- 
marked  result,  which  was  shown  at  operation  to  be  due 
to  an  invasion  of  the  pancreas  by  the  growth. 

{d)  Test  for  Fat-splitting  Ferment  in  the  Urine  (Opie) . — 
This  test  has  only  been  employed  by  Opie  in  one  case  of 
acute  haemorrhagic  pancreatitis,  and  there  he  obtained 
evidence  that  the  urine  contained  a  fat-splitting  ferment. 
We  have  had  no  experience  with  it  in  acute  pancreatitis, 
and  are  not  acquainted  with  any  published  accounts  of 


336       The  Pancreas:  Its  Surgery  and  Pathology 

cases  in  which  it  has  been  tried.  If  future  experience 
should  confirm  Opie's  observation,  and  show  that  fat- 
splitting  ferments  are  constantly  present  in  acute  pan- 
creatitis, a  most  useful  addition  will  have  been  made  to 
our  means  of  diagnosing  the  condition. 

(e)  Indicanuria. — An  increased  excretion  of  indican 
and  ethereal  sulphates  in  the  urine  has  been  considered, 
by  some  writers,  as  an  indication  of  disease  of  the  pan- 
creas. There  are  others,  however,  who  have  advanced 
reasons  why  the  excretion  of  these  substances  should  be 
diminished.  There  is  no  doubt  that  in  many  cases  an 
abnormal  amount  of  indican  is  found  in  the  urine,  but 
in  our  experience  there  is  just  as  frequently  no  excess, 
and  it  is  probable  that  the  condition  of  the  urine  with 
regard  to  this  substance  is  dependent  upon  factors  of 
which  the  condition  of  the  pancreatic  secretion  is  only  one, 
and  that  not  the  most  important.  Indicanuria  is  not, 
therefore,  of  any  great  value  in  the  diagnosis  of  diseases 
of  the  pancreas,  and  the  same  may  be  said  of  an  increase 
in  the  proportion  of  ethereal  sulphates. 

(/)  Rediiction  in  the  Excretion  of  Phosphates. — A  reduced 
amount  of  phosphates  in  the  urine  when  on  a  milk  diet, 
owing  to  non-splitting  of  the  nuclein  constituent  of  the 
caseinogen,  has  been  noted  in  cases  of  pancreatic  disease 
associated  with  a  diminution  or  absence  of  the  secretion. 
In  order  that  this  test  may  be  applied  it  is  necessary 
that  the  patient  should  be  placed  upon  a  milk  diet  for 
several  days,  and  that  a  regular  estimation  of  the  phos- 
phates in  the  total  excretion  of  each  twenty-four  hours 
should  be  made.  Since  the  excretion  of  phosphates  is  also 
diminished  in  pneumonia  and  other  acute  febrile  diseases, 
in  chronic  and  acute  nephritis,  and  in  gout  and  during 
pregnancy,  these  must  first  be  excluded,  and  it  is  advisable . 
that  the  diminution  should  be  shown  to  be  dependent 
upon  failure  of  the  pancreatic  secretion  by  watching  the 


General  Symptomatology  and  Diagnosis        337 

effects  produced  by  the  administration  of  preparations 
of  pancreas  with  the  food. 

(g)  Oxaluria. — A  well-marked  deposit  of  calcium  oxa- 
late crystals  has  been  found  in  63  yev  cent,  of  our  cases 
of  chronic  pancreatitis,  and,  although  we  do  not  lay  much 
stress  upon  it  as  an  aid  to  diagnosis,  such  a  deposit  may 
be  regarded  as  tending  to  confirm  evidence  obtained  by 
other  means. 

Qi)  Lipuria. — The  presence  of  fat  globules  in  the  urine 
has  been  noted  in  a  few  cases  of  pancreatic  disease.  It  is 
such  a  rare  occurrence,  however,  and  may  be  due  to  so 
many  different  causes,  that  it  is  to  be  regarded  rather  as  a 
curiosity  than  as  a  diagnostic  sign  of  any  practical  value. 

{i)  Fat  Necrosis. — The  recognition  of  fat  necrosis  by 
the  surgeon  who  opens  the  abdomen  to  relieve  symptoms 
associated  with  peritonitis  in  its  upper  part,  is  of  the 
utmost  importance,  as,  in  practically  all  cases,  it  may  be 
taken  to  indicate  a  grave  lesion  of  the  pancreas,  probably 
haemorrhagic,  gangrenous,  or  suppurative  inflammation. 
It  is  said  not  to  occur  generally  with  suppurative  inflam- 
mation, but  in  a  case,  to  be  referred  to  subsequently,  most 
extensive  fat  necrosis  was  found  with  a  subdiaphragmatic 
abscess  of  pancreatic  origin.  It  has  also  been  said  that 
the  presence  of  extensive  fat  necrosis  is  a  fatal  sign,  but 
this  is  not  invariably  so,  for  Truhart  has  collected  ten  cases 
in  which  the  diagnosis  was  made,  and  yet  an  immediately 
fatal  issue  did  not  follow,  and  we  have  had  the  opportunity 
of  observing  one  case  in  which  complete  recovery  took 
place  after  operation  in  a  patient  with  acute  pancreatitis 
in  whom  fat  necrosis  was  well-marked  and  diffuse. 

4.  Special  Symptoms  Obtained  by  Artificial  Means.— (a) 
Alimentary  Glycosuria. — If  100  grams  of  grape-sugar  be 
given  in  a  quarter  of  a  litre  of  water  or  tea  to  a  normal 
individual  in  the  morning,  fasting,  an  examination  of  the 
urine  two  or  three  hours  subsequently  will  show  that  it 
has  not  given  rise  to  glycosuria,  but  if,  for  any  reason. 


7,2)8       The  Pancreas:  Its  Surgery  and  Pathology 

the  metabolic  functions  of  the  pancreas  are  at  fault  a 
more  or  less  marked  reaction  for  sugar  will  be  obtained. 
The  production  of  alimentary  glycosuria  in  this  way  does 
not,  however,  necessarily  indicate  that  there  is  a  gross 
lesion  of  the  pancreas,  for  it  may  result  from  toxic  changes 
such  as  are  probably  present  in  acute  febrile  diseases 
and  alcoholism,  and  a  similar  result  may  be  obtained  in 
cases  of  neurasthenia,  traumatic  necrosis,  acute  diseases 
of  the  brain  and  meninges,  in  many  forms  of  mental  debil- 
ity, especially  mania  and  paralysis,  in  exophthalmic 
goitre,  and  in  some  diseases  of  the  liver,  not  necessarily 
associated  with  obvious  changes  in  the  pancreas.  The 
observations  of  Wille,  however,  show  that  in  some  65 
per  cent,  of  cases  in  which  alimentary  glycosuria  occurs 
a  grave  pancreatic  disease  is  present.  Many  investiga- 
tors have  made  use  of  cane-sugar  in  applying  this  test, 
but  it  is  not  so  suitable  for  the  purpose  as  dextrose,  or 
fruit-sugar,  as  the  results  are  not  so  simple  and  easy  to 
interpret,  for  the  glycosuria  following  the  administration 
of  cane-sugar  may  be  due  to  anomalies  of  fermentation 
and  absorption  in  the  intestine. 

(6)  SahWs  Test. — This  well-known  method  of  diagno- 
sis depends  upon  the  fact  that  if  iodoform  be  enclosed  in 
gelatin  capsules,  hardened  in  formalin,  and  given  by  the 
mouth,  it  is  almost  unaffected  by  gastric  digestion,  but  is 
readily  dissolved  by  the  pancreatic  secretion.  If  there- 
fore pancreatic  digestion  is  normal,  iodine  should  appear 
in  the  urine  and  saliva  in  from  four  to  eight  hours;  the 
absence  of  the  reaction,  or  its  delayed  appearance,  if 
the  motor  functions  of  the  stomach  be  normal,  indicates, 
according  to  Sahli,  an  impairment  of  pancreatic  digestion. 

The  great  and  apparently  insurmountable  difficulty  in 
this  method  is  to  strike  a  degree  of  hardness  for  the  cap- 
sules suitable  in  all  cases.  Formalin  has  the  property  of 
making  all  tissues  on  which  it  acts  proof  against  digestion, 
tryptic  as  well  as  peptic,  and  it  is  therefore  necessary 


General  Symptomatology  and  Diagnosis        339 

that  the  capsules  should  only  be  acted  on  long  enough 
to  protect  them  against  digestion  in  the  stomach,  but  not 
for  a  sufficient  length  of  time  to  prevent  their  solution 
by  the  more  active  pancreatic  secretions.  This  in  itself 
is  a  difficult  matter,  but  when  it  is  remembered  that  nor- 
mally there  are  individual  variations  in  peptic  and  tryptic 
digestion  the  difficulty  is  still  further  increased.  Ex- 
perience has  proved  that  these  objections  are  not  merely 
theoretical,  for  Fromme,  Wallenfang,  and  Sahli  himself 
have  stated  that,  from  a  retarded  reaction,  the  diagnosis 
of  disturbed  pancreatic  function  cannot  always  be  made 
with  certainty.  A  prompt  reaction,  however,  appears 
to  exclude  any  serious  lesion  of  the  gland.  The  results 
of  Sahli 's  test  have  therefore  only  a  negative  value  in 
diagnosis. 

(c)  Test  Meals. — Since  1879,  when  Van  den  Valden 
drew  attention  to  the  fact  that  free  hydrochloric  acid 
was  absent  from  the  stomach  contents  in  carcinoma  of 
the  pylorus,  it  has  been  recognised  that  a  chemical  exami- 
nation of  the  gastric  secretion  was  of  considerable  assis- 
tance in  the  diagnosis  of  malignant  disease  of  the  stomach. 
But  in  April,  1905,  Moore,  Alexander,  Kelly,  and  Roaf 
extended  this  proposition  by  stating  that  an  examination 
of  the  stomach  contents,  obtained  about  one  hour  after 
the  administration  of  Ewald's  test  meal  of  a  pint  of  tea 
without  milk  or  sugar  and  a  round  of  dry  toast,  showed 
striking  diminution  or  entire  absence  of  the  hydrochloric 
acid  normally  present  after  such  a  meal,  in  cancer  situated 
in  other  parts  of  the  body,  such  as  the  breast,  uterus, 
tongue,  etc.  Subsequent  observers  have  not  obtained 
quite  such  remarkable  and  constant  results  as  those 
quoted  by  Moore  and  his  fellow-workers  in  their  original 
paper,  but  there  is  no  doubt  that  a  marked  diminution 
in  the  amount  of  hydrochloric  acid  in  the  stomach  con- 
tents is  frequently  met  with  in  such  cases,  and  that, 
taken  in  conjunction  with  other  symptoms,  it  may  often 
be  of  assistance  in  diagnosis. 


340       The  Pancreas:  Its  Surgery  and  Pathology 

The  differentiation  of  malignant  disease  of  the  pancreas 
from  chronic  pancreatitis  is,  in  some  instances,  so  difficult 
that  any  method  that  holds  promise  of  assistance  is  worthy 
of  a  careful  trial.  We  have  only  had  the  opportunity  of 
examining  a  test  meal  from  three  cases  of  cancer  of  the 
pancreas,  and  have  obtained  the  following  results: 

Case      I.     (No.  662.) 

Phloroglucin-vanillin    reaction    for    free 

HCl , Negative 

Total  acid  (as  HCl) 0.007% 

Physiologically  active  HCl 0.000% 

Case    II.     (No.  749.) 

Phloroglucin-vanillin    reaction    for    free 

HCl Negative 

Total  acid  (as  HCl) 0.05% 

Physiologically  active  HCl 0.00% 

Case  III.     (No.  780.) 

Phloroglucin-vanillin    reaction    for    free 

HCl Negative 

Total  acid  (as  HCl) 0.009% 

Physiologically  active  HCl 0.000% 

It  will  thus  be  seen  that  not  only  was  there  absence 
of  free  hydrochloric  acid  in  all  these  cases,  but  no  evidence 
of  physiologically  active  hydrochloric  acid  (as  estimated 
by  Willcox's  method)  could  be  found.  For  the  sake  of 
comparison  we  may  quote  another  case,  which,  although 
the  results  of  the  "pancreatic  reaction"  pointed  to  sim- 
ple inflammation,  was  so  much  like  malignant  disease, 
both  clinically  and  at  operation,  that  a  guarded  prognosis 
was  given.  The  patient,  however,  rapidly  improved  after 
the  operation  and  is  now  quite  well : 

Case  IV.     (No.  639.) 

Phloroglucin-vanillin    reaction    for    free 

HCl Deep  crimson 

Total  acid  (as  HCl) 0.13% 

Physiologically  active  HCl 0.13% 

In  this  instance  there  was  an  abundance  of  free  hydro- 
chloric acid,  and  the  percentage  of  physiologically  active 


General  Symptomatology  and  Diagnosis        341 

acid  was  not  suVjnormal,  in  marked  contrast  to  their  entire 
absence  in  the  other  three  cases.  Our  experience  is  as 
yet  too  small  to  permit  of  any  dogmatic  statement  being 
made,  but  it  is  sufficient  to  show  that  the  results  of  a 
chemical  examination  of  a  test  meal,  when  taken  in  con- 
junction with  other  evidence,  may  prove  of  considerable 
help  in  diagnosis. 

With  such  a  number  of  signs  and  symptoms  as  those 
above  enumerated  it  is  difficult  to  understand  how  the 
idea  has  gained  so  firm  a  hold  that  disease  of  the  pancreas 
is,  as  a  rule,  unrecognisable  during  life.  Although,  in 
any  particular  case,  one  may  not  meet  with  all  of  them, 
there  is  usually  such  a  combination  that,  with  care,  no 
difficulty  need  be  experienced  in  arriving  at  a  satisfactory 
conclusion.  Different  diseases  of  the  pancreas,  as  one 
would  expect,  present  very  various  groupings  of  symp- 
toms, but  in  all  digestive,  metabolic,  and  physical  signs 
can  be  found  that  will  indicate  the  true  source  of  those 
alterations  in  well-being  of  which  the  patient  complains. 
In  every  case  the  past  history  of  the  patient  should  be 
carefully  gone  into  for  evidence  of  chronic  dyspepsia, 
gall-stone  attacks,  and  recent  infectious  diseases,  such  as 
typhoid  fever,  influenza,  etc.,  all  of  which  may  be  followed 
by  diseases  of  the  pancreas.  Then,  having  investigated 
the  present  condition  of  the  case  as  regards  loss  of  weight, 
alterations  of  appetite,  especially  an  objection  to  meat  and 
fat,  nausea,  vomiting,  and  pain  in  the  upper  abdominal 
region  radiating  under  the  left  scapula,  the  presence  or 
absence  of  jaundice  should  be  noticed,  particularly  in  the 
sclerotics,  and  the  pancreatic  region  should  be  examined 
for  a  tumour  and  for  tenderness  on  pressure.  It  should 
now  be  possible  to  determine  whether  the  pancreas  is 
probably  diseased  or  not,  and  to  decide  whether  the 
assistance  of  the  clinical  pathologist  is  required  to  further 
investigate  the  case. 

In  all  cases  of  suspected  pancreatic  trouble  it  is  advis- 
able that    a  complete  chemical    and   microscopical   ex- 


342       The  Pancreas:  Its  Surgery  and  Pathology 

amination  of  the  faeces  and  urine  should  be  made  by 
a  competent  observer,  for  the  results  of  such  examina- 
tions will,  in  the  large  majority  of  cases,  clinch  the 
diagnosis.  The  fseces  should  be  examined  as  fresh  as 
possible,  for  their  reaction  may  quickly  change,  and  the 
presence  of  an  acid  reaction  is  suggestive  of  pancreatic 
trouble.  An  excess  of  unabsorbed  fat  in  the  motions 
points  to  disease  of  the  pancreas,  particularly  if  this  is 
chiefly  due  to  a  high  proportion  of  neutral  fat.  Azotor- 
rhoea,  along  with  steatorrhoea,  tends  still  further  to  con- 
firm the  diagnosis.  Complete  absence  of  stercobilin  from 
the  f^ces  is  suggestive  of  malignant  disease  of  the  pan- 
creas, while  its  presence  points  to  obstruction  of  the  com- 
mon duct  by  gall-stones. 

In  investigating  the  urine  a  thorough  examination 
should  be  made  for  albumin,  sugar,  acetone  bodies, 
indican,  bile,  and  urobilin;  the  urea,  chlorides,  and  phos- 
phates should  be  estimated  quantitatively;  and  the 
centrifugalised  deposit  examined  for  calcium  oxalate 
crystals.  Sahli's  test  and  Opie's  test  for  fat-splitting 
ferments  may  be  tried,  and  in  all  cases  it  is  advisable 
to  perform  Cammidge's  "pancreatic"  reaction.  The 
presence  of  sugar  in  the  urine,  along  with  evidence  of 
disease  of  the  pancreas,  is  of  great  value,  and,  even 
when  sugar  is  absent  naturally,  its  discovery  after  the 
administration  of  a  test  dose  of  loo  grams  of  glucose 
tends  to  confirm  the  diagnosis  of  disease  of  the  pan- 
creas. The  acetone-bodies  point  to  abnormal  tissue  waste, 
such  as  is  met  with  in  serious  cases  of  pancreatitis  and 
cancer  of  the  pancreas,  and  an  excessive  amount  of  in- 
dican, although  not  diagnostic  of  disease  of  the  pancreas, 
may  indicate  the  site  of  the  infection  from  which  a  chronic 
inflammation  has  arisen.  Bile-pigments  in  the  urine 
show  that  there  is  obstruction  of  the  biliary  passages, 
and  a  pathological  excess  of  urobilin  points  to  catarrh  of 
the  bile-duct,  and  possibly  of  the  pancreatic  duct,  which 
may  or  may  not  be  associated  with  a  floating  biliary 


General  Symptomatology  and  Diagnosis        343 

calculus.  A  diminished  excretion  of  phosphates,  when 
the  patient  is  on  a  milk  diet,  is  indicative  of  a  pancreatic 
lesion,  and  a  diminution  of  chlorides  relative  to  urea  is 
met  with  in  serous  effusions  such  as  occur  in  malignant 
disease.  A  well-marked  deposit  of  oxalate  crystals  tends 
to  confirm  a  diagnosis  of  chronic  pancreatitis.  Sahli's 
test,  when  negative,  is  strongly  against  there  being  serious 
disturbance  of  the  functions  of  the  pancreas,  and  the 
presence  of  fat-splitting  ferment  in  the  urine  probably 
indicates  acute  pancreatitis. 

We  have  found  the  "pancreatic"  reaction  of  very 
great  assistance  in  all  cases  of  suspected  pancreatic 
disease,  but  we  are  not  prepared  to  contend  that  it  is 
pathognomonic  or  infallible,  for  even  the  most  com- 
monly relied  upon  tests  are,  it  is  well  known,  liable 
to  prove  misleading  at  times,  unless  due  regard  is  paid 
to  possible  sources  of  fallacy,  and  the  results  are  in- 
terpreted in  the  light  of  clinical  evidence.  As  we  have 
pointed  out,  it  is  not  impossible  that  inflammatory  and 
degenerative  changes  in  other  pentose-containing  tissues 
of  the  body  may  at  times  give  rise  to  a  positive  "  pancre- 
atic" reaction,  but,  having  regard  to  the  relatively  large 
proportion  of  this  substance  contained  in  the  pancreas, 
disease  of  that  organ  is  the  most  likely,  and  probably  the 
most  common,  cause  of  such  a  result.  In  making  a 
diagnosis  in  suspected  cases  of  pancreatic  disease,  or  of 
jaundice  in  which  it  is  sought  to  determine  whether  there 
is  a  gross  obstruction  to  the  free  flow  of  bile  and  pancreatic 
juice  into  the  intestine,  and  whether  this  obstruction, 
when  present,  is  of  a  simple  or  malignant  nature,  it  is 
important  to  remember  that  the  "pancreatic"  reaction 
is  only  one  factor  that  has  to  be  taken  into  account,  and 
that,  although  it  may  afford  valuable  evidence,  for  or 
against,  it  is  necessary  that  its  indication  should  be  con- 
sidered with  the  clinical  symptoms,  and  that,  whenever 
possible,  they  should  be  checked  by  a  chemical  analysis 
of  the  faeces. 


344       The  Pancreas:  Its  Surgery  and  Pathology 

Finally,  if  there  is  a  suspicion  of  malignant  disease, 
Ewald's  test  breakfast  may  be  given,  and  the  stomach 
contents  examined  in  an  hour  for  free  and  physiologically 
active  hydrochloric  acid. 

Literature 

V.  Ackeron:   Berliner  klin.  Wochensch.,  1889,  Nr.  14. 

Battersby:   Gaz.  med.  de  Paris,  1844,  pp.  219,  617;  Arch.  gen.  de  med., 

1844. 
Biondi:  Riforma  med.,  1896,  ii,  Nr.  9,  p.  97. 
Bright:   Med.  Associat.  Trans.,  1838,  p.  18. 
Bull:    New  York  Med.  Journ.,  1887,  p.  376. 
Cammidge:  Arris  and  Gale  Lect.,  Lancet,  March  19,  1904.     Brit.  Med. 

Journ.,  Oct.  25,  1905.     Tr.  Roy.  Med.  Soc.  1906. 
Capparelli:  Arch.  ital.  de  Biol.,  1894,  xxi,  398. 
Chari:   Wiener  med.  Wochenschr.,  1880,  xxx,  139. 
Cowley:  Lond.  Med.  Journ.,  1788. 
Demme:  Wiener  med.  Blatter,  1884,  Nr.  51. 
Fitz:   Congress  of  Amer.  Phys.  and  Surg.,  May,  1903. 
Fles:   Holland  Arch.,  1864,  ii,  187. 
Fromme:   Miinch.  med.  Wochensch.,  1901,  Nr.  15. 
Goodman:   Phila.  Med.  Trans.,  xxii,  6,  1878. 
Gould:  Anat.  Museum  of  Boston.  1847,  P-  ^47- 
Gould:    Soc.  for  Med.  Inform.,  1847,  P-  217.     Lancet,    1891,  ii,    290. 

Brit.  Med.  Journ.,  1894,  i,  1191. 
Hirschfeld:    Zeitsch.  f.  klin.  Med.,   1896,  xxxi,  212;     189 1,  xix,  249. 
Holzmann:   Miinchener  med.  Wochensch.,  1894,  Nr.  20. 
Kuntzmann:  Hufeland's  Journal,  1820. 
Ktister:  Berliner  klin.  Woch.,  1887,  S.  154;  Deutsch.  med.  Woch.,  1887, 

S.  189  u.  216. 
Leichtenstern :     Handb.    d.    spec.    Therap.    von    Penzoldt-Stintzung, 

1896,  iv,  203. 
Lichtheim:   Berliner  klin.  Wochenschr.,  1894,  Nr.  8. 
Ludolph:   Dissertation,  1890. 

Minnich:   Berliner  klin.  Wochenschr.,  1894,  S.  187. 
Moore,  Alexander:  Kelly  and  Roaf,  Lancet,  April  29,  1905,  p.  1120. 
Le  Nobel:  Maly's  Jahresb.,  1886,  S.  449. 
Opie:    "Diseases  of  the  Pancreas,"  1903. 
Oser:    Nothnagel's  "Encycl.  of  Pract.  Med."  ("Dis.  of  Pancreas  and 

Liver"),  1903. 
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Robson,  Mayo:    Hunterian  Lecture,  1904.     Address  before  Canadian 

Med.  Assoc,  1904.      Polyclinic  Lecture,  Lancet,  1900.     Address 

before  Amer.  Surg.  Assoc,  1902. 
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klin.  Med.,   1904,  Ixi,  383.     Berliner   klin.  Wochenschr.,   1902, 

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Willcox:   Lancet,  June  10,  1905,  p.  1566. 
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Ziehl:  Deutsch.  med.  Wochenschr.,  1883    Nr.  37. 


CHAPTER    XIII 

INJURIES 

The  pancreas  is  more  securely  protected  from  direct 
violence  than  almost  any  other  abdominal  organ.  In- 
juries are  therefore  comparatively  rare,  and,  when  they 
do  occur,  are  almost  invariably  accompanied  by  more  or 
less  damage  of  other  viscera.     Garre  was  only  able  to 


Inferior 
vena  cava    Aorta 


Stomach 


Left  adrenal 


Right  adrenal 


Right 
kidnej' 


Kidney 


Colon 


Fig.  115.- — Diagram  showing  the  relations  of  the  pancreas. 


meet  with  thirty  recorded  cases,  and  in  but  eight  was 
the  pancreas  the  only  organ  injured.  Recovery  occurred 
in  three  cases.  In  addition  to  the  anterior  wall  of  the 
abdomen,  there  lie  in  front  of  the  pancreas  the  transverse 

345 


346       The  Pancreas:  Its  Surgery  and  Pathology 

colon,  the  stomach,  and  the  omentum,  while  behind  are 
the  aorta  and  inferior  vena  cava,  the  second  lumbar  verte- 
bra, with  the  adjoining  portions  of  the  first  and  second 
vertebrae  in  the  middle  line,  and  the  psoas  and  the  quad- 
ratus  lumborum  muscles  and  the  thick  mass  of  the  erector 
spinas,  with  many  fascial  strata,  laterally.  The  pancreas 
thus  occupies  almost  the  centre  of  the  body,  and  any 
harmful  influence  coming  from  without  must  first  encoun- 
ter other  more  superficial  structures. 

Injuries  of  the  pancreas  may  be  divided  into:  (i)  Lac- 
erations due  to  direct  violence;  (2)  bullet  wounds ; 
(3)  penetrating  wounds  and  stabs. 


(I)    LACERATIONS  DUE  TO  DIRECT  VIOLENCE 

In  the  majority  of  these  cases  the  force  producing  the 
injury  has  been  directed  from  before  backwards  at  the 

epigastrium,  and  has 
been  of  such  severity 
that  other  organs  within 
the  ab  dominal  cavity 
have  been  damaged  at 
the  same  time.  A  rent 
in  the  liver,  a  tear  of 
the  kidney  or  spleen,  a 
rupture  of  the  duodeno- 
jejunal flexure  or  duode- 
num, a  laceration  of  the 
stomach,  or  extensive  in- 
jury to  the  peritoneum 
have  all  been  observed. 
In  most  of  the  earlier  re- 
corded cases  the  injury 
to  the  pancreas  was  only 
recognised  after  death,  and  was  accompanied  by  one  or 
other  of  the  lesions  mentioned,  but  even  in  some  of 
these  the  injury  to  the  pancreas  was  so  much  greater 


Fig.  116. — Traumatic  rupture  of 
the  pancreas  and  bruising  of  the  duo- 
denum, followed  by  hasmatemesis  and 
fat  necrosis  (Santos). 


Injuries 


347 


than  that  inflicted  on  other  organs  that  it  was  proVjably 
the  cause  of  the  fatal  issue.  The  number  of  recorded 
examples  of  injuries  of  the  pancreas  is  probably  not  a 
correct  indication  of  the  frequency  with  which  they  occur, 
for  when  an  injury  of  the  gland  forms  only  a  part  of  a 
multijjle  visceral  disorganisation  due  to  violence  it  is  apt 


Fig.  iiy.- — Showing  the  rupture  in  the  duodenum.  The  ends  have 
been  filled  with  cotton-wool  and  separated  from  one  another  for  the  pur- 
pose of  demonstration. 


to  be  overlooked,  even  after  death,  as  the  hsemorrhage 
from  a  ruptured  liver,  spleen,  or  kidney  is  so  profuse  as 
to  rapidly  fill  the  peritoneal  cavity. 

Laceration  of  the  pancreas  is  most  commonly  due  to 
the  patient  being  run  over,  and  fatal  cases  arising  from 
this  cause  have  been  reported  by  Travers,  Stoerk,  Cooper, 


348       The  Pancreas:  Its  Surgery  and  Pathology 

Pressel,  and  Hale  White.  In  all  of  these  the  injury  of 
the  pancreas  was  accompanied  by  fracture  or  laceration 
of  ribs,  liver,  kidneys,  or  other  organs.  In  a  fatal  case 
recorded  by  Wilks  and  Moxon,  however,  where  the  pan- 
creas was  so  crushed  opposite  the  spinal  column  as  to  be 


Fig.  ii8. — Shows  the  rupture  in  the  pancreas  and  its  peritoneal  cover- 
ing. 


divided  into  two  parts,  the  laceration  was  unaccompanied 
by  other  abdominal  injuries,  and  the  specimen  shown  in 
Fig.  119,  from  St.  Bartholomew's  Hospital  Museum,  was 
also  taken  from  a  patient  in  whom  post-mortem  the 
pancreas  was  the  only  organ  found  to  be  injured.  In  the 
latter  .case  the  patient  had  been  crushed  between  two 


Injuries 


349 


vans,  and  on  admission  only  complained  of  slight  pain 
in  the  epigastrium.  Twenty-four  hours  later  he  became 
collapsed,  but  recovered.  Subsequently  he  vomited, 
became  seriously  collapsed,  and  died  three  days  after  the 
receipt  of  the  injury.  At  autopsy  a  rupture  of  the  pan- 
creas dividing  it  into  two  nearly  equal  portions  was  found ; 
there  was  fat  necrosis  in  the  neighbourhood,  but  no 
injury  of  the  duodenum,  liver,  spleen,  kidneys,  or  other 
abdominal  viscera.  Fatal  cases  of  laceration  of  the 
pancreas  following  a  kick  have  been  described  by  Jaun, 


Uninjured  pancreas 


Spleen 


Rupture  and  hsemorrhage  into  pancreas 

Fig.  1 19.— -Rupture  of  the  pancreas,  without  any  other  abdominal  in- 
jury (St.  Bartholomew's  Hosp.  Museum,  2276  D). 

Leith,  and  Groeningen.  In  Jaun's  case  there  was  no 
other  abdominal  injury.  An  injury  of  the  pancreas 
that  caused  death  on  the  fourth  day  was  produced,  in 
a  case  reported  by  Wagstaff ,  by  a  fall  from  a  cart  on  to 
the  left  side.  Post-mortem  the  other  abdominal  viscera 
were  found  to  be  uninjured.  Goldmann,  Villiers,  and 
Hale  White  have  reported  instances  in  which  fatal  injury 
of  the  pancreas,  accompanied  by  more  or  less  extensive 
damage  of  other  abdominal  organs,  has  followed  a  blow 
in  the  upper  epigastric  region.     In  most  instances  the 


350        The  Pancreas:  Its  Surgery  and  Pathology 

chief  injury  has  been  opposite  the  spinal  column,  the 
pancreas  being  probably  caught  and  compressed  thereon 
by  the  crushing  force. 

Although  injury  of  the  pancreas  is  usually  brought 
about  by  severe  violence,  the  tissues  of  the  gland  are  so 
soft  and  easily  bruised  that  slight  injuries  have  more 
effect  upon  it  than  upon  firmer  organs.  The  following 
case,  observed  by  one  of  us,  illustrates  the  serious  results 
that  may  follow  from  a  comparatively  slight  blow  over 
the  region  of  the  pancreas : 

A  butler  slipped  and  fell  forward  against  a  knifeboard 
projecting  from  the  end  of  the  table  at  which  he  was 
working.  The  blow  was  comparatively  slight  and  the 
man  did  not  even  fall  to  the  ground.  Pancreatitis  fol- 
lowed on  what  was,  at  the  beginning,  probably  a  mere 
bruising  of  the  pancreas,  but  which  was  succeeded  by  slight 
bleeding  into  the  gland,  and,  this  effusion  becoming  in- 
fected, acute  haemorrhagic  pancreatitis  resulted.  An 
exploration  for  the  cause  of  the  pancreatitis  resulted  in 
the  discovery  of  a  large  collection  of  highly  blood-stained 
fluid  in  the  lesser  peritoneal  sac,  some  of  which  had 
burst  through  a  small  laceration  in  the  omentum  into 
the  greater  peritoneal  sac.  There  was  general  periton- 
itis present  at  the  time  of  operation,  and  though  drainage 
was  freely  adopted,  both  from  the  front  and  back,  the 
patient  did  not  survive  many  hours. 

A  case  of  considerable  interest  and  importance  has 
been  described^  in  which  pressure  from  a  tourniquet 
caused  severe  bruising  of  the  pancreas.  The  patient 
had  an  aneurysm  of  the  abdominal  aorta,  not  far  from  its 
bifurcation,  and  an  attempt  was  made  to  treat  it  by  the 
application  of  a  tourniquet  nearer  the  heart.  In  the  few 
hours  during  which  the  patient  survived  the  application 
of  the  instrument,  no  symptoms  referable  to  the  pancreas 
were  observed,  but  post-mortem  the  gland  was  found  to 
be  much  bruised  where  it  lay  across  the  vertebral  column. 

^  Lancet,  Feb.  4.  1905. 


Injuries  351 

In  a  second  class  of  injuries  due  to  crushes  and  blows, 
although  the  pancreatic  lesion  is  less  profound  than  in 
those  just  referred  to,  it  is  the  main  result  of  the  injury, 
and  slowly  gives  rise  to  symptoms  that  may  be  relieved 
by  operation.  After  the  shock  of  the  accident  has  passed 
off,  the  patient  may  appear  to  have  quite  recovered,  but 
in  a  longer  or  shorter  time,  varying  from  a  few  days  to 
several  weeks,  an  abdominal  tumour  appears,  which  on 
being  explored  proves  to  be  a  distension  of  the  lesser  sac 
by  blood-stained  fluid.  The  first  case  of  this  kind  was 
recorded  by  Kiilenkampff ,  and  others  have  been  reported 
by  Senn,  Kiister,  Karewski,  etc.  Cases  following  a  blow 
have  been  described  by  Ross,  Hadra,  Lloyd,  Randall, 
Karewski,  and  one  of  us,  by  Littlewood  after  a  kick,  by 
W.  H.  Brown  after  a  crush,  and  by  Cathcart  and  Sheen 
after  the  patients  had  been  run  over.  Coombs  and  Nash 
have  tabulated  the  records  of  twenty-five  cases,  including 
a  few  in  which  the  swelling  has  followed  vomiting  or  some 
other  form  of  straining.  "  The  sequence  of  events  in  such 
cases  is  probably  that  the  traumatism  causes  a  laceration 
of  the  posterior  layer  of  the  lesser  sac  and  of  the  pancreas, 
to  which  it  is  intimately  adherent.  Blood,  and  possibly 
some  pancreatic  secretion,  are  then  poured  into  the  lesser 
sac  and  peritonitis  results.  The  foramen  of  Winslow  is 
sealed  by  adhesion,  and  the  lesser  cavity  of  the  peritoneum, 
now  a  closed  sac,  is  distended  with  serous  fluid  mixed 
with  blood  and  pancreatic  secretion.  When  the  fluid  is 
evacuated  the  pancreas  continues  to  pour  its  secretion 
into  the  lesser  sac  through  the  rent  in  its  peritoneal  invest- 
ment. ' '  (Mayo  Robson  and  Moynihan,  p.  5 1 . )  The  rela- 
tion of  these  tumours  to  the  pancreas,  and  the  presence  in 
their  contents,  and  in  the  fluid  issuing  from  the  drainage- 
tube,  of  ferments,  has  led  to  their  being  generally  spoken 
of  as  pancreatic  cysts,  but  they  are  now  regarded  as  one 
of  the  varieties  of  pseudo-cysts  of  the  pancreas,  and  will 
be  considered  in  that  connection  in  a  subsequent  chapter. 


352       The  Pancreas:  Its  Surgery  and  Pathology 

Symptoms  and  Diagnosis. — In  the  first  class  of  cases, 
where  the  injury  to  the  pancreas  is  great,  but,  as  a  rule, 
only  constitutes  one  of  the  results  of  the  accident,  there 
has  been  profound  collapse  coming  on  rapidly  or,  as  in 
the  cases  reported  by  Jaun,  Wagstaff,  and  Leith,  after 
an  interval  of  an  hour  or  more.  The  immediate  symp- 
toms of  shock  are  due  to  the  hemorrhage,  but  when  they 
appear  after  a  latent  interval  are  to  be  ascribed  to  the 
complications  arising  from  the  injury  to  the  pancreas. 
According  to  Leith,  the  absence  of  all  external  signs  of 
injury  of  the  abdomen  is  surprising  and  noteworthy. 
The  absence  of  any  definite  signs  pointing  to  pancreatic 
injury  renders  an  accurate  diagnosis  impossible  in  such 
cases,  and  it  has  usually  only  been  at  the  post-mortem 
examination  that  the  source  of  the  haemorrhage,  etc., 
have  been  traced.  When,  however,  from  the  gravity  of 
the  collapse,  the  site  of  the  injury,  and  the  presence  of 
dulness  in  the  right  or  left  flank,  it  is  evident  that  there 
is  some  serious  visceral  lesion  with  internal  hemorrhage, 
speedy  operation  is  indicated,  and  may  prove  successful 
in  saving  the  patient's  life,  even  when  there  is  extensive 
laceration  of  the  pancreas,  as  in  the  case  recorded  by 
Randall. 

Where  the  symptoms  of  shock  are  less  severe,  and  the 
patient  recovers,  but  later  develops  a  cystic  swelling  in 
the  region  of  the  pancreas,  the  diagnosis  is  less  difficult, 
and  operation  may  be  undertaken  with  every  prospect  of  a 
successful  issue.  The  nature  of  the  contents  of  such  a 
cystic  swelling  may  afford  evidence  of  its  origin  from  an 
injury  of  the  pancreas  by  the  discovery  of  ferments. 
The  fluid  may  be  clear,  or  turbid  from  the  presence  of 
blood,  and  is  alkaline  in  reaction.  It  has  a  specific 
gravity  of  i.oio  to  1.0120,  and  usually  contains  albumin 
and  nucleo-proteids.  Starch-splitting  and  fat-splitting 
ferments  are  present,  and  can  be  recognised  by  the  tests 
described  on  page  264.     As  a  rule,  it  has  no  digestive 


Injuries  353 

power  for  proteids,  for  it  has  not  been  activated  by  con- 
tact with  enterokinase,  but  feeble  proteolytic  powers 
may  be  shown,  such  as  are  possessed  by  the  juices  of 
many  tissues.  The  accelerating  action  of  salts  of  calcium, 
etc.,  on  the  proteolytic  activities  of  pancreatic  juice,  dem- 
onstrated by  Delezenne,  may  account  for  the  presence  of 
a  more  marked  digestive  power  in  some  instances.  Where 
the  swelling  forms  quickly,  direct  laceration  of  the  pan- 
creas is  indicated,  but  where  it  forms  slowly,  may  be 
after  some  months  or  even  years,  it  is  probably  due  to 
pancreatitis  following  the  injury,  with  effusion  into  the 
lesser  sac.  The  appearance  of  a  swelling  which  rapidly 
reaches  a  certain  bulk,  and  then  remains  stationary, 
suggests  the  outpouring  of  fluid  into  a  preformed  sac 
produced  by  closure  of  the  foramen  of  Winslow  by  ad- 
hesions previous  to  the  injury.  The  swelling  occupies 
the  epigastric,  umbilical,  and  left  hypochondriac  regions. 
The  stomach  and  transverse  colon  can  be  detected  in 
front,  and  the  descending  colon  behind  and  to  the  left. 

Treatment. — The  immediate  shock  and  collapse  con- 
sequent on  the  accident  having  been  treated  by  the 
means  usually  adopted  in  such  cases,  a  satisfactory  reac- 
tion on  the  part  of  the  patient  raises  the  question  of  oper- 
ative interference.  Where  there  is  evidence  of  internal 
hemorrhage  this  should  be  undertaken  at  once,  and  an 
attempt  made  to  secure  the  bleeding  points.  Experi- 
mental work  has  shown  that  wounds  of  the  pancreas  can 
be  sutured,  and  that  healing  speedily  takes  place,  so  that 
if  a  laceration  of  the  gland  be  found  it  should  be  dealt 
with  by  accurately  coapting  the  edges  by  sutures,  care 
being  taken,  however,  to  avoid  puncturing  the  main 
duct  of  the  gland.  The  cases  in  which  such  surgical 
intervention  is  possible  are,  unfortunately,  few,  as  the 
injury  to  the  pancreas  is  most  frequently  only  part  of  a 
wide-spread  destruction  involving  the  liver,  kidneys, 
spleen,  stomach,  or  intestine.  In  the  case  reported  by 
23 


354       The  Pancreas:  Its  Surgery  and  Pathology 

Randall,  referred  to  previously,  operation  six  hours  after 
the  accident  was  followed  by  recovery. 

The  patient  had  been  crushed  between  the  pole  of  a 
van  and  another  vehicle  in  the  epigastric  region.  He 
had  violent  pain,  became  faint  and  collapsed,  and  vom- 
ited. On  admission  to  hospital  an  hour  later,  he  was 
found  to  be  still  collapsed,  with  a  small  weak  pulse  of 
90  and  a  temperature  of  95°  F.  He  was  treated  with 
stimulants,  warmth,  and  a  hypodermic  injection  of  half 
a  grain  of  morphin.  Midway  between  the  ensiform 
cartilage  and  the  umbilicus  there  was  a  bruise  nearly 
two  inches  in  diameter  and  very  tender  to  the  touch. 
The  abdomen  moved  with  respiration,  but  was  very  tender, 
especially  above  the  navel.  The  liver  dulness  was  nor- 
mal, but  there  was  marked  dulness  in  the  right  flank. 
The  urine  showed  no  abnormality.  At  the  operation 
no  gas  was  found  in  the  peritoneum,  but  there  was  much 
clotted  and  fluid  blood.  No  lesion  of  the  liver,  stomach, 
or  bowels  could  be  found.  A  large  tear,  directed  verti- 
cally, and  running  from  the  stomach  to  the  liver,  was 
seen  in  the  gastrohepatic  omentum,  and  there  was  a  tear 
in  the  peritoneum  over  the  pancreas.  Under  this  was 
a  tear  in  the  body  of  the  gland  two  inches  long,  running 
from  the  right  and  below  tipwards  and  to  the  left,  leaving 
a  loose,  tongue-like  process  of  gland  substance,  the  base 
of  which  was  half  the  width  of  the  organ.  On  passing 
a  finger  through  the  tear  it  came  directly  upon  the  aorta. 
There  was  free  oozing,  but  no  large  blood-vessels  could 
be  found.  The  rent  in  the  pancreas  was  sewn  up  by  four 
silk  stitches,  and,  after  the  lesser  peritoneal  sac  had  been 
cleansed,  the  greater  part  of  the  tear  in  the  gastro-hepatic 
omentum  was  sewn  up  with  a  continuous  catgut  suture, 
space  being  left  for  drainage.  The  abdomen  having  been 
thoroughly  flushed  with  hot  saline  solution,  an  iodoform 
gauze  packing  was  inserted  down  to  the  pancreas  and  the 
rest  of  the  abdominal  wound  closed.  For  the  first  three 
days  the  patient  was  constantly  sick  and  in  much  pain. 
He  later  developed  delusions,  but  slowly  recovered, 
gaining  in  weight  and  strength,  and  was  discharged,  ten 
weeks  after  the  operation,  with  the  wound  healed.  On 
one  occasion  the  urine  contained  a  small  quantity  of 


Injuries  355 

sugar,  but  it  quickly  disappeared.  No  special  features 
were  noticed  in  the  motions.  The  discharge  from  the 
wound  consisted  of  a  viscid,  slightly  turbid  fluid,  which 
caused  excoriation  of  the  margins  of  the  wound.  A 
fortnight  after  the  operation  it  was  noticed  that  the  skin 
over  the  abdomen  and  lower  part  of  the  thorax  resembled 
that  produced  by  an  extensi\'e  burn  of  the  first  and  third 
degrees. 

A  somewhat  similar  case  in  which  recovery  followed 
prompt  operation  has  been  reported  by  Karewski.  The 
patient  had  been  run  over  after  being  struck  in  the  abdo- 
men by  the  shaft  of  a  vehicle.  He  was  able  to  walk 
home,  but  abdominal  pain  coming  on  shortly  afterwards 
an  exploratory  laparotomy  was  performed.  There  was 
a  large  quantity  of  blood,  especially  in  the  region  of  the 
gastrocolic  ligament,  and  the  head  of  the  pancreas  was 
found  to  be  crushed.  The  patient  lost  400  grams  of  pure 
pancreatic  juice  daily  through  the  fistula  and  diminished 
in  weight,  but  the  secretion  diminished  on  a  fatty  anti- 
diabetic diet  and  the  fistula  was  eventually  closed. 

The  treatment  of  the  cystic  swellings  following  injury 
of  the  gland  will  be  discussed  under  Cysts  of  the  Pancreas. 

(2)  BULLET  WOUNDS 

Cases  of  bullet  wounds  of  the  pancreas  have  been 
described  by  Otis,  Sanitas,  Niemann,  Bertram,  Von  Bra- 
mann,  Hahn,  Nini,  Borchardt,  Simmonds,  Mann,  Korte, 
Slavsky,  Carnell,  Jephson,  Becker,  and  Kindt.  Rarely 
the  pancreas  has  been  the  only  abdominal  organ  injured, 
but  in  the  majority  of  instances  other  organs  have  also 
been  involved  in  the  injury.  Otis,  in  his  surgical  report 
on  the  American  Civil  War,  relates  three  cases.  In  one 
the  pancreas  and  spleen  were  both  lacerated,  and  the 
splenic  artery  was  divided.  The  patient  lived  a  month. 
In  the  second  the  patient  lived  fifteen  days,  and  the  sto- 
mach, as  well  as  the  pancreas,  was  found  to  have  been 


356       The  Pancreas:  Its  Surgery  and  Pathology 

wounded.  In  the  third  the  lung,  the  liver,  and  the  pan- 
creas were  all  injured.  The  patient  lived  but  twelve 
days.  The  late  President  McKinley  was  wounded  in  the 
stomach,  pancreas,  and  left  kidney.  Ninni  reports  a 
case  of  revolver  wound  of  the  abdomen  in  which  there 
was  a  wound  of  the  pancreas,  six  of  the  small  intestine, 
and  one  in  the  colon  at  the  hepatic  flexure,  but  in  which 
the  patient  recovered  after  operation,  and  left  the  hospital 
thirty-five  days  after  admission.  In  a  case  of  revolver 
wound  of  the  pancreas,  associated  with  double  perfora- 
tion of  the  stomach,  recorded  by  Kindt,  widely  dissemi- 
nated fat  necrosis  was  found  post-mortem,  and  a  similar 
condition  has  also  been  noted  in  two  other  cases  after 
death,  but  has  not  been  recorded  as  present  in  any  of  the 
cases  at  operation.  The  organ  most  commonly  injured 
with  the  pancreas  has  been  the  stomach  (nine  cases), 
then  the  liver  (seven  cases),  the  lesser  omentum  (four 
cases),  the  diaphragm  (three  cases),  the  spleen,  small 
intestine,  and  large  intestine  each  in  two,  and  the  lung, 
kidney,  heart,  and  portal  vein  each  in  one  instance. 

Symptoms. — There  are  no  pathognomonic  signs  of 
injury  of  the  pancreas  in  bullet  wounds  of  the  abdomen, 
and  even  suggestive  symptoms  are  usually  absent.  The 
probable  course  of  the  bullet,  as  indicated  by  the  site  of 
entry  and  exit,  is  usually  the  only  guide.  When  the 
abdomen  is  opened  and  neighbouring  viscera  are  found 
to  be  wounded,  particularly  the  posterior  wall  of  the 
stomach  and  lesser  omentum,  it  is  essential  that  a  careful 
search  should  be  made  for  any  injury  of  the  pancreas. 

Treatment. — Operation  should  be  undertaken  as  speed- 
ily as  possible  in  all  cases.  Any  bleeding  points  should 
be  secured,  and  a  careful  but  rapid  search  made  for 
injury  to  the  stomach,  intestine,  liver,  etc.  The  wound 
of  the  pancreas  may  be  sutured,  but,  if  there  is  much 
laceration,  it  may  be  necessary  to  resect  a  portion  of  the 
gland  and  unite  the  clean-cut  edges  by  sutures.     Care 


Injuries  357 

must  be  taken  to  avoid  the  main  duct,   the   superior 
mesenteric  artery,  and  the  portal  vein.     Complete  dis- 
organization of  the  gland  can  only  be  treated  by  plugging 
and  drainage,  for  it  is  practically  impossible  to  remove  it, 
and  the  attempt  is  not  justifiable  on  physiological  grounds. 
Where    suture   is    possible    drainage    should    always   be 
adopted,  for  there  is  invariably  a  certain  amount  of  leak- 
age, and  if  an  exit  is  not  provided  for  the  exuding  secretion, 
local  disturbances  and  peritonitis  may  result.     It  is  note- 
worthy that  in  two  cases  where  an  injury  of  the  pancreas 
was  sutured,  but  no  drainage  was  provided,  a  localised 
destruction  of  tissue  was  foimd  post-mortem.     Drainage 
has  usually  been  provided  through  the  abdominal  wound, 
but  a  posterior  opening,  such  as  Jephson  adopted  in  his 
case,  and  was  also  carried  out  by  one  of  us  in  another 
instance,   is   probably  more   efficient.     It   is   frequently 
stated  that  wounds  of  the  pancreas  are  almost  always 
fatal,   but  this  is  not  necessarily  the  case,   if  suitable 
operative  measures  are  quickly  taken.     Of  the  twenty- 
one  cases  of  injury  of  the  pancreas  due  to  gunshot  wounds 
of  which  we  have  found  records,  fifteen  were  operated  on 
and  nine  of  these  recovered  (Bramann — two,  Hahn,  Nini, 
Borchardt,  Slavsky,  Jephson,  Otis,  and  Becker).     Of  the 
six  in  which  death  occurred,  the  injury  of  the  pancreas 
was  not  discovered  in  three,  so  that  in  nine  out  of  twelve 
instances  it  may  be  considered  that  the  operation  saved 
the  patient's  life,  for  all  but  one  of  the  cases  in  which 
operation  was  not  resorted  to  died. 

(3)  PENETRATING  WOUNDS 

Penetrating  wounds  due  to  stabs  or  cuts  with  a  knife 
or  bayonet  have  been  reported  by  Kleburg,  Laborderie, 
Caldwell,  Dargau,  and  Kiittner.  In  the  cases  described 
by  all  but  Kiittner,  the  pancreas  protruded  through  the 
wound,  and  was  either  returned  or  the  projecting  portion 
removed.     Recovery  followed  in  all.     In  Ktittner's  case 


358       The  Pancreas:  Its  Surgery  and  Pathology 

there  was  an  abdominal  wound,  14  cm.  long,  through 
which  protruded  the  stomach,  transverse  colon,  and  several 
loops  of  small  intestine.  At  the  operation,  a  quarter 
of  an  hour  after  the  receipt  of  the  injury,  the  anterior 
wall  of  the  stomach  was  found  to  have  been  injured,  the 
left  border  of  the  liver  was  notched,  the  lesser  omentum 
was  cut,  and  the  pancreas  had  been  transfixed  just  to  the 
left  of  the  tuber  omentale.  Venous  and  arterial  blood 
were  welling  up  from  the  wound  in  the  pancreas,  but 
this  was  checked  by  two  deep  and  one  superficial  catgut 
suture  in  the  parenchyma  of  the  gland.  The  bursa 
omentalis  was  plugged  and  the  stomach  wound  sutured. 
The  patient  recovered,  although,  at  first,  he  was  gravely 
ill  with  symptoms  of  threatened  collapse  and  subphrenic 
abscess. 

Treatment. — The  treatment  of  penetrating  wounds 
of  the  pancreas  is  exactly  on  the  same  lines  as  those 
described  for  gunshot  wounds,  and  what  has  been  said 
under  that  heading  equally  applies  here. 

SEQUELS 

The  sequels  of  injuries  of  the  pancreas  may  be  seen  in 
the  gland  itself,  or  are  shown  by  changes  in  the  neigh- 
bouring tissues.  The  effects  produced  by  injury  of  the 
pancreas,  with  closure  of  the  foramen  of  Winslow,  and 
the  conversion  of  the  lesser  peritoneal  sac  into  a  cystic 
cavity,  have  already  been  referred  to.  The  injury  may 
also  produce  a  true  cyst  of  the  pancreas,  either  from 
bruising  and  tearing  of  the  duct,  causing  stenosis  and  an 
accumulation  of  secretion  behind  the  point  of  injury,  or 
the  duct  may  be  compressed  and  distorted  by  the  scar 
tissue  resulting  from  the  injury  to  the  neighbouring  gland 
substance.  Cases  in  which  inflammatory  changes  in  the 
gland  have  resulted  from  injury  have  been  recorded 
by  Wandesleben,  Rolleston,  and  others.  In  Rolleston's 
case  an  abscess  in  the  head  of  the  pancreas,  with  fat 


Injuries  359 

necrosis  in  the  subperitoneal  cavity,  was  found  at  the 
post-mortem,  eighty  days  after  a  blow  in  the  abdomen 
which  had  given  rise  to  pain,  vomiting,  inaction  of  the 
bowels,  and  collapse  simulating  intestinal  obstruction. 
Hansemann,  Fitz,  and  Prince  have  described  cases  of 
necrosis  of  the  pancreas  after  injury.  A  wound  of  the 
abdominal  wall  has,  in  some  cases,  been  followed  by  pro- 
trusion of  the  pancreas.  The  possibility  of  such  an 
occurrence  has  been  doubted,  but  there  is  now  indisput- 
able evidence  that  such  a  complication  may  occur.  The 
original  case  of  "prolapse  of  the  pancreas"  recorded  by 
Laborderie  was  proved  by  microscopical  examination 
of  the  protruding  tissue  to  be  in  reality  a  case  of  prolapsed 
omentum,  but  well  authenticated  cases  have  been  since 
reported  by  Otis  (two),  Kleberg,  Caldwell,  Dargau,  Allen, 
Thompson,  and  Pereira-Guimaraes.  The  failure  of  Labor- 
derie to  recognise  the  nature  of  the  tissue  in  his  case  by 
naked-eye  inspection  emphasises  the  necessity  of  a  care- 
ful microscopical  examination  in  every  instance. 

Literature 

Allen:  American  Weekly,  1876,  p.  305. 

Becker:   Zent.  f.  Chir.,  1905,  Nr.  5. 

Bertram:   Inaug.  Dissert.,  Jena,  1893. 

Borchardt:   Berlin,  klin.  Woch.,  Jan.,  1904,  Nr.  3. 

V.  Bramann:   Arch.  f.  klin.  Chir.,  1899-1900,  Ix,  482. 

Brown,  W.  H.:   Lancet,  1894,  i,  21. 

Caldwell:  Transylvan.  Journ.  of  Med.,  1828,  i,  116. 

Carnell:  Annals  of  Surgery,  xli,  724. 

Cathcart:  Edinburgh  Med.  Journ.,  July,  1890. 

Coombs  and  Nash:   Lancet,  1901,  i,  1826. 

Cooper:   Lancet,  1839. 

Dargau:  Med.  and  Surg.  Report.,  Aug.  22,  1874. 

Delegenne:   Brit.  Med.  Journ.,  Dec.  22,  1906,  p.  1785. 

Fitz:  Truhart,  "Pankreas  Path.,"  S,  332. 

Goldmann:   Quoted  by  Korte,  Deut.  Chir.,  1870. 

Groennigen:   Rep.  Berlin  Garrison  Hosp.,  1890. 

Hadra:    New  York  Med.  Rec,  1896.     Amer.  Journ.  Med.  Sci.,  1897, 

i.  III. 
Hahn:   Deut.  Zeit.  f.  Chir.,  Iviii,  1900-1901. 
Hansemann:   Truhart,  "Pankreas  Path.,"  1887,  obs.  160. 
Jaun:   Indian  Annals  of  Med.  Sci.,  1855. 
Jephson:_  Quoted  by  Connel,  Annals  of  Surg.,  xli,  724. 
Karewski:  Deutsche  med.  Woch.,  1890,  No.  46.     Med.  Press,  March  6, 

1907. 


360       The  Pancreas:  Its  Surgery  and  Pathology 

Kindt:  Gaz.  des  Hopital,  April  4,  1905. 

Kleburg:  Archiv.  f.  klin.  Chir.,  1868,  S.  523.  __ 

Korte:   Verhandl.  der  Freien.  Chir.  Verein,  xiii,  87. 

KiilerLkampff :   Berliner  klin.  Wochenschr.,  1882,  Nr.  7. 

Kuster:    Berlin,  klin.  Wochenschr.,  1887,  S.  154.     Deut.  med.  Woch., 

1887,  S.  189  u.  215.  _ 
Ktittner:   Beitr.  z.  klin.  Chir.,  1901,  xxxii,  244. 
Laborderie:   Gaz.  des  Hopital,  1856,  No.  2  and  9. 
Leith:  Lancet,  1895,  i,  770.     Edinb.  Med.  Journ.,  Nov.,  1895. 
Littlewood:   Lancet,  1892,  i,  871. 

Lloyd,  Jordan:  Lancet,  Nov.,  1892.     Brit.  Med.  Journ.,  1892,  ii,  105 1. 
Mann:  American  Med.,  Oct.  19,  1901. 
Nini:  Cent.  f.  Chir.,  1901,  No.  41,  p.  1024. 

Otis:   "Med.  and  Surg.  History  of  the  War  of  the  Rebellion,"  ii,  2,  159. 
Pereira-Guiamaraes :   Quoted  by  Oser,  Nothnagel's  "Encycl.  of  Pract. 

Med.,"  1903,  p.  269. 
Prince:   Boston  Med.  and  Surg.  Journ.,  1882,  p.  28. 
Pressel:   Inaug.  Dissert.,  Berlin,  1895. 
Randall:  Lancet,  Feb.,  1905,  p.  291. 
RoUeston:  Brit.  Med.  Journ.,  1892,  ii,  895. 
Rose:  Deut.  Zeitschr.  f.  Chir.,  xxxiv,  3,  36. 
Sanitas:   "Rep.  of  German  Army  in  War,"  1870-187 1. 
Senn:    Trans,  of  Amer.  Med.  Assoc,   1886.     Amer.  Journ.    of   Med. 

Sci._,  1885. 
Sheen:  Clin.  Journ.,  Nov.  8,  1899;  Ibid.,  March  29,  1905,  p.  381. 
Simmonds:   Miin.  med.  Woch.,  1898,  No.  6,  S.  169. 
Slavsky:   Roussky  Vratch,  July  31,  1904. 
Stoerk:   "Annus  Medicus,"  1836. 

Thompson:  Quoted  by  Senn,  "Surgery  of  the  Pancreas,"  p.  34. 
Travers:  Lancet,  1827. 
Villiere:    Bull.  d.  1.  Soc.  Anat.,  1895. 
Wagstaff :   Lancet,  1895,  i. 

Wandesleben:   Wochenschr.  f.  d.  gesam.  Halk.,  1S45. 
White,  Hale:   Guy's  Hosp.  Reports,  liv. 
Wilks  and  Moxon:    "Path.  Anat.,"  second  and  third  edits. 


CHAPTER  XIV 
INFLAMMATORY  AFFECTIONS  OF  THE  PANCREAS 

Catarrh  and  Suppurative  Catarrh  of  the  Pancreas 

If  we  were  to  base  our  opinions  on  the  post-mortem 
records  of  the  past,  inflammatory  affections  of  the  pan- 
creas would  have  to  be  reckoned  among  the  rarest  of  dis- 
eases, but  recent  clinical  observations  and  operative 
experience  show  that  such  conclusions  would  be  far  from 
accurate,  and  that  inflammatory  aft'ections  of  the  pan- 


Fig.  1 20. — "Enlarged  and  hard  pancreas" — probably  a  case  of  chronic 
pancreatitis  (Baillie). 


creas,  or  its  ducts,  are  very  much  more  common  than  is 
generally  supposed. 

Historical  References. — When  studying  the  subject  of 
pancreatitis,  in  the  light  of  modern  pathological  know- 
ledge, it  behoves  us  to  bear  in  mind  that  the  older  pathol- 
ogists had  noticed  and  described  the  naked-eye  appear- 

361 


362       The  Pancreas:  Its  Surgery  and  Pathology 

ances  of  nearly  all  the  conditions  that  are  engaging  so 
much  of  our  attention  at  the  present  time.  Tulpius,  so 
far  back  as  1672,  describes  a  diffuse  pancreatitic  abscess 
of  pyaemic  origin,  and  Matthew  Baillie,  physician  to  St. 
George's  Hospital,  in  a  work  on  "Morbid  Anatomy," 
published  in  1799,  describes  what  he  calls  a  hard  pancreas 
with  the  lobules  distinct,  but  which  is  what  we  now  should 
call  a  case  of  chronic  interstitial  pancreatitis.  He  also 
figures  in  the  same  volume  a  case  of  pancreatic  calculi, 
most  carefully  dissected,  showing  the  relation  of  the  bile 
and  pancreatic  ducts.  Portal  in  1804  described  a  case  of 
acute  suppurative  pancreatitis  following  on  an  attack  of 
gout  in  the  feet,  and  Percival,  in  18 18,  described  a  well- 
marked  case  of  pancreatic  abscess  associated  with  jaun- 
dice. The  following  is  a  quotation  from  a  paper  by  Dr. 
W.  J.  Mayo  before  the  American  Surgical  Association, 
the  executive  committee  of  which  approved  of  it  for  pub- 
lication: "  Balzer  in  1879  first  described  acute  pancrea- 
titis with  fat  necrosis.  Little  attention  was  attracted 
to  the  subject,  however,  and  it  was  not  until  Fitz  ten 
years  later  wrote  his  classical  papers  that  the  medical 
world  really  became  aware  of  the  inflammatory  diseases 
of  the  pancreas.  Fitz  soon  after  pointed  out  the  fact 
that  many  supposed  cysts  of  the  pancreas  due  to  trauma- 
tism were  really  accumulations  of  fluid  in  the  lesser  cavity 
of  the  peritoneum  and  the  omental  bursse.  A  proper 
understanding  of  chronic  pancreatitis  has  been  largely 
due  to  Robson,  who  first  noticed  the  disease  in  connexion 
with  his  operative  work  upon  the  biliary  tract.  In  fact, 
the  surgical  study  of  the  inflammatory  diseases  of  the 
pancreas  may  be  said  to  be  the  result  of  an  inquiry  into 
the  causation  of  some  of  the  complications  of  gall-stone 
disease." 

Classification. — Pancreatic  inflammations  may  be  catar- 
rhal, in  which  the  inflammatory  trouble  is  in  the  ducts,  or 
parenchymatous,  in  which  the  substance  of  the  pancreas 


Inflammatory  Affections  of  the  Pancreas        363 

is  involved.  The  former  resemble  the  different  forms  of 
cholangitis,  with  which,  indeed,  they  are  frequently 
associated;  the  latter  bear  more  resemblance  to  inflam- 
matory affections  of  the  appendix,  "  suppurative  and 
gangrenous  appendicitis."  The  following  shows  the 
classification  at  a  glance : 


(A)  Catarrhal  Inflammations: 

(a)  Simple  catarrh     |   , 

'^chronic. 

(b)  Suppurative  catarrh. 

(c)  Pancreo-lithic  catarrh. 

(B)  Parenchymatous  Inflammations: 
Acute : 

(a)  Hsemorrhagic  pancreatitis. 
.  Ultra-acute,  in  w^hich  the  hasmorrhage 

precedes  the  inflammation,  the  bleed- 
ing being  profuse,  and  both  within  and 
outside  the  gland. 
I  2.  Acute,  in  which  inflammation  precedes 
I  the  hasmorrhage,  which  is  less  profuse 
I  and  is  distributed  in  patches  through 
I       the  gland. 

(b)  Gangrenous  pancreatitis. 

(c)  Suppurative  pancreatitis   (diffuse  suppura- 
tion) . 

Subacute : 

Abscess  of  the  pancreas  (not  diffuse  suppuration) . 
Chronic : 

(a)   Interstitial  pancreatitis. 
f  I .  Interlobular, 
I  2 .  Interacinar. 
(6)  Cirrhosis  of  the  pancreas. 

Etiology. — The  etiology  of  pancreatitis  may  be  classified 
under  predisposing  and  exciting  causes. 


364       The  Pancreas:  Its  Surgery  and  Pathology 

Among  the  predisposing  causes  are : 

(a)  Obstruction  in  the  ducts,  the  result  of  gall- 
stones, duodenal  catarrh,  pancreatic  calculi, 
cancer  of  the  papilla  or  of  the  head  of  the  pan- 
creas, ulcer  of  the  duodenum,  followed  by 
cicatricial  stenosis  of  the  papilla,  ascarides 
and  lumbrici,  etc. 

(b)  Injury  either  from  a  bruise,  as  by  manipula- 
tion in  operating,  or  from  a  crush,  as  by  a  blow 
in  the  epigastrium,  or  from  wounding  by  a 
sharp  instrument. 

(c)  Haemorrhage  into  the  gland. 

(d)  General  ailments,  such  as  typhoid  fever,  in- 
fluenza, and  mumps. 

(e)  Certain  anatomical  peculiarities  in  the  pancreas 
or  its  ducts. 

(/)    Atheroma,  or  fatty  degeneration,  of  the  blood- 
vessels.    Back-pressure  from  disease  of  the 
heart,  lungs,  etc. 
(g)   New-growth,  e.  g.,  cancer  or  sarcoma. 
The  chief  exciting  causes  are : 

1 ,  Infection  conveyed : 

(a)  From  the  blood,  as  in  syphilis  or  pyaemia. 

(6)  From  the  duodenum,  as  in  gall-stone  obstruc- 
tion or  gastro-intestinal  catarrh. 

(c)  By  extension  inwards  from  adjoining  organs, 
as  in  gastric  ulcer  or  cancer  eroding  the  pan- 
creas. 

2.  Irritation,  as  in  alcoholism  (doubtful). 

The  anatomy  of  the  pancreas,  with  its  ducts  opening 
into  a  portion  of  the  intestine  never  free  from  organisms, 
is  the  key  to  the  etiology  of  pancreatitis,  but  even  so, 
were  it  not  that  the  common  bile-duct  and  the  pancreatic 
duct  are  so  closely  related  the  pancreas  would  probably 
generally  escape.     It  is  well  known  that  even  aseptic 


Inflammatory  xA.ffcctions  of  the  Pancreas        365 

ligature  of  the  common  bile-duct  opens  the  way  to  the 
presence  of  organisms  within  the  bile-ducts,  and  we  have 
very  definite  proof  that  a  gall-stone  in  the  common  duct 
is  very  shortly  followed  by  infective  cholangitis,  which 
may,  in  unfavourable  circumstances,  become  suppurative 
cholangitis  and  lead  to  abscesses  in  the  liver  or  to  other 
secondary  troubles.  But  in  28.5  per  cent,  of  cases  (Tes- 
tut)  the  common  bile  and  pancreatic  ducts  open  together 
into  the  ampulla  of  Vater,  which  itself  opens  into  the 
duodenum,  and,  according  to  Helly,  in  62  per  cent,  of 
cases  the  common  bile-duct  is  intimately  embraced  by 
the  pancreas,  so  that  when  a  gall-stone  passes  down  the 
bile-duct  it  must,  of  necessity,  in  a  large  proportion  of 
cases,  compress  the  pancreatic  duct  and  cause  a  damming 
back  of  its  secretion,  which,  arguing  from  analogy  as  well 
as  from  practical  experience  of  the  troubles  that  follow, 
means  damming  back  an  infected  secretion.  Thus  it  is 
brought  about  that  in  many  cases  of  common-duct  chole- 
lithiasis, w^here  the  calculus  reaches  the  pancreatic  por- 
tion of  the  duct,  and  remains  there  for  some  time,  catar- 
rhal inflammation  of  the  pancreas  occurs.  If  the  stone 
passes  after  a  short  period  the  pancreatitis  may  subside 
and  leave  no  trace,  or  the  swelling  of  the  pancreas  may 
persist  and,  for  a  time,  keep  up  pressure  on  the  com^mon 
bile-duct,  leading  to  a  persistence  of  the  jaundice,  though 
there  is  no  concretion  left  to  cause  obstruction,  nor  any 
evidence  of  disease  of  the  liver  beyond  the  jaundice  due 
to  the  mechanical  obstruction.  Thus  may  be  explained 
some  of  the  cases  of  chronic  jaundice  with  so-called  biliary 
catarrh. 

If,  however,  the  gall-stone  obstruction  persists  for 
some  time,  and  the  patient's  health  is  feeble  or  becomes 
seriously  deteriorated,  what  was  at  first  merely  a  simple 
catarrh  may  become  a  suppurative  one,  and  as  the  same 
process  involves  the  liver  and  the  pancreas  the  ducts  of 
b)Oth  become  filled  with  pus.     We  have  now  suppurative 


366       The  Pancreas:  Its  Surgery  and  Pathology 

catarrh  of  the  pancreatic  ducts  associated  with  a  suppura- 
tive cholangitis,  a  very  serious,  and  generally  a  fatal, 
condition. 

If  the  suppurative  catarrh  persists  unrelieved,  it  may 
lead,  not  only  to  abscesses  in  the  liver,  but  also  to  ab- 
scesses in  the  pancreas,  and  possibly,  in  case  of  survival, 
to  subacute  pancreatitis,  as  in  cases  to  be  described  under 
abscess  of  the  pancreas.  If  the  suppurative  catarrh 
takes  on  an  acute  course  the  condition  may  become  one 
allied  to,  and  unrecognisable  from,  pyaemia,  as  in  a  case 
to  be  related  later. 

If  the  infective  catarrhal  condition  persists,  and  does 
not  assume  the  more  dangerous  suppurative  form,  or 
even  if  simple  obstruction  of  the  pancreatic  duct  persists 
from  any  cause  with  only  mild  infection,  we  may  have  an 
almost  analogous  condition  to  the  one  occurring  in  the 
liver  that  produces  cirrhosis.  In  this  more  chronic  form 
interstitial  pancreatitis  occurs,  which  in  an  early  stage 
may  be  arrested  by  the  removal  of  the  cause,  as  will  be 
shown  when  considering  chronic  pancreatitis.  The  chronic 
pancreatitis  is  of  the  interlobular  variety,  and  conse- 
quently does  not  involve  the  islands  of  Langerhans  until 
a  late  stage,  when  the  organ  may  become  cirrhotic  and 
diabetes  supervenes. 

If  a  small  gall-stone  happens  to  descend  into  an  unusu- 
ally large  diverticulum  of  Vater  and  to  lodge  there,  it  will 
make  a  through  channel  from  the  common  bile-duct,  as 
shown  in  the  diagram  (Figs.  60  and  61),  and  this  Opie  has 
shown  to  be  a  cause  of  acute  pancreatitis,  the  bile  being 
forced  direct  into  the  pancreas.  In  one  case  under  the 
care  of  Dr.  Halsted  this  condition  occurred  and  acute 
hsemorrhagic  pancreatitis  ensued.  Opie  states  that  he 
has  produced  acute  hcemorrhagic  pancreatitis  in  dogs  by 
injecting  bile  into  the  pancreatic  duct.  Other  irritating 
substances,  suspensions  of  bacteria,  and  various  acids  and 
alkalies  have  the  same  effect,  and  have  been  considered 
in  detail  in  the  chapter  on  pathology. 


Inflammatory  Affections  of  the  Pancreas        367 

It  is  quite  clear,  therefore,  that  gall-stones  in  the  com- 
mon duct  are  a  frequent,  in  fact,  by  far  the  most  frequent, 
cause  of  the  various  forms  of  pancreatitis,  but  the  ana- 
tomical conditions  just  mentioned,  though  evidently 
potent,  are  certainly  not  necessary  for  the  production  of 
acute  pancreatitis,  which  may,  as  is  well  known,  occur 
apart  from  cholelithiasis.  Any  gall-stone  or  stones  im- 
pacted in  the  pancreatic  portion  of  the  duct,  or  even 
filling  the  ampulla  of  Vater,  may  be  efficient  causes  of 
the  trouble. 

It  may  be  asked,  Why  should  not  every  case  of  common 
duct  cholelithiasis  be  complicated  by  pancreatic  inflamma- 
tion ?  This  is  readily  explained  by  the  fact  that  in  a  cer- 
tain percentage  of  cases  the  common  bile-duct  and  the 
pancreatic  duct  open  by  separate  orifices  into  the  duode- 
num, while  in  another  percentage  the  duct  of  Santorini 
is  either  the  principal  outlet  for  the  pancreatic  secretion 
or  is  of  such  a  size  that  it  can  act  as  an  efficient  outlet 
even  if  Wirsung's  duct  becomes  obstructed.  The  condi- 
tion described  by  Opie,  where  the  ampulla  of  Vater  is 
very  large  and  a  small  gall-stone  becomes  impacted  at  its 
orifice,  is  only  rarely  found ;  otherwise  acute  pancreatitis 
would  be  more  common  owing  to  overwhelming  of  the 
pancreatic  ducts  by  infected  bile. 

Besides  gall-stones  the  other  factors  mentioned  may 
lead  to  obstruction  of  the  pancreatic  ducts,  to  infection 
of  the  pent-up  secretion,  and  to  the  different  varieties  of 
pancreatitis,  the  rationale  of  the  process  being  similar 
to  the  one  sketched  above.  It  is  possible  that  infec- 
tion may  extend  upwards  from  the  duodenum  without 
preliminary  obstruction,  apparently  by  continuity  of 
mucous  membrane,  catarrhal  pancreatitis  being  then  a 
sequel  of  gastro-duodenal  catarrh. 

In  case  of  injury,  in  whatever  way  inflicted,  it  seems 
not  unreasonable  to  think  that  the  soft  glandular  sub- 
stance will  readily  yield  and  so  set  free  the  auto-destruc- 


368       The  Pancreas:  Its  Surgery  and  Pathology 

tive  secretion  of  the  gland,  which  by  dissolving  the  walls 
of  the  blood-vessels  will  lead  to  further  haemorrhage, 
and  then  to  the  collection  of  a  quantity  of  easily  decom- 
posable material  that  only  needs  infecting  to  become 
acutely  dangerous.  The  contiguity  of  the  stomach  and 
intestines  furnishes  the  possibility  of  infection,  though 
if  infection  does  not  take  place  the  injury  may  be  repaired 
as  in  other  organs.  This  probably  explains  acute  pan- 
creatitis supervening  not  immediately  but  some  days 
after  an  injury. 

Haemorrhage  into  the  pancreas,  so-called  pancreatic 
apoplexy,  arising  from  diseased  vessels,  or  in  some  other 
way,  by  disrupting  the  gland,  may  lead  to  pancreatitis, 
as  in  the  case  recently  reported  to  the  Societe  de  Chirurgie 
by  M.  Guinard.^  That  haemorrhage  into  the  pancreas 
does  not  always  give  rise  to  pancreatitis  is  shown  by  the 
presence  of  old  blood-stains  in  cases  dying  from  other 
causes,  and  it  is  reasonable  to  argue  that  some  other 
factor  is  necessary.  M.  Guinard  is  of  opinion  that  in  his 
case  the  mercurial  treatment  played  a  part  in  the  etiology 
of  the  condition,  for,  just  as  mercury  produces  saliva- 
tion, it  is  possible  that  it  may  act  upon  the  pancreas  in  an 

^  A  man  aged  thirty-five,  for  several  days  had  been  reUeved  by  in- 
jections of  the  benzoate  of  mercury  for  a  specific  orchitis.  After  the 
tenth  injection  he  suddenly  felt  a  sharp  stabbing  pain  in  the  epigastric 
region;  it  was  so  acute  that  several  hypodermics  of  morphine  failed  to 
give  relief.  During  the  following  days  the  patient  had  fetid  diarrhoea, 
and  a  srnall  tumour  appeared  in  the  epigastric  region.  It  was  diag- 
nosed as  a  gumma,  and  the  mercurial  infections  were  continued ;  but  the 
patient  continued  to  have  great  pain,  with  continued  diarrhoea  and 
complete  intolerance  for  food;  he  lost  flesh  to  an  alarming  extent,  and 
became  cachectic.  When  M.  Guinard  was  called  in  he  found  him  almost 
moribund.  To  the  left  of  the  Hnea  alba,  between  the  umbilicus  and  the 
costal  margin,  there  was  a  tumour  of  the  size  of  a  man's  fist,  smooth, 
shining,  almost  fluctuating,  dullish  on  percussion.  An  exploratory 
puncture  gave  issue  to  sticky  blood.  From  the  sudden  onset  of  the 
attack,  the  intense  pain,  the  rapid  cachexia,  and  the  absence  of  fever, 
M.  Guinard  diagnosed  haemorrhagic  pancreatitis,  and  performed  lap- 
arotoniy.  He  found  a  large  blackish  retrogastric  tumour,  from  which 
on  incision  a  large  quantity  of  fluid  blood  mixed  with  clots  escaped. 
It  was  a  haematic  cyst  of  the  pancreas.  A  drain  was  put  in,  and  cure 
was  rapid.  On  awakening  from  the  anesthetic  the  epigastric  pains  had 
disappeared.  The  contents  of  the  cyst  were  found  to  be  absolutely 
aseptic. 


Inflammatory  Affections  of  the  Pancreas        369 

analogous  way,  giving  rise  to  mercurial  pancreatism  with 
intense  congestion  of  the  gland  and  interstitial  haemor- 
rhage. It  has  also  to  be  remembered  that  the  patient 
was  a  syphilitic  subject.  Infection  of  the  disorganised 
tissues  probably  plays  an  important  part  in  the  conver- 
sion of  a  simple  haemorrhage  into  the  acute  fulminating 
inflammatory  condition  in  many  instances,  and  the  amount 
and  situation  of  the  blood  have  also,  no  doubt,  an  im- 
portant influence  on  the  result. 

In  general  ailments,  such  as  typhoid  fever,  influenza, 
etc.,  the  well-known  predilection  of  typhoid  bacilli  for 
the  biliary  passages  would  afford  an  easy  explanation  of 
their  access  to  the  pancreas,  and,  though  it  is  difficult  to 
prove,  in  several  cases  of  catarrhal  inflammation  of  the 
pancreas  a  history  pointing  strongly  to  influenza  and  to 
typhoid  fever  as  the  cause  has  been  obtained.  In  one 
case  the  relationship  was  proved  by  the  discovery  of 
typhoid  bacilli. 

As  to  mumps  and  pancreatitis  there  seems  to  be  some 
peculiar  and  intimate  relationship  between  the  salivary 
glands  of  the  mouth  and  the  abdomen,  and  in  the  case 
of  a  young  adult  coming  under  the  observation  of  one  of 
us  some  years  ago,  it  seemed  highly  probable  that  a 
metastasis  occurred  about  the  third  day  of  the  disease, 
when  the  pain  and  distress  almost  completely  left  the 
face  and  were  followed  by  violent  epigastric  pain  and 
alarming  symptoms  of  depression,  accompanied  by  sick- 
ness and  fever,  which  then  rapidly  passed  off,  after  three 
days'  anxiety,  and  were  followed  by  orchitis.  M.  Simo- 
nin  gave  the  result  of  his  observations  on  652  cases  of 
mumps  treated  in  the  military  hospital  of  Val  de  Grace. 
In  ten  cases,  or  1.3  per  cent.,  there  were  symptoms  of 
pancreatitis  which  occurred  from  the  first  to  the  twelfth 
day  of  the  disease  and  lasted  from  two  to  seven  days,  the 
principal  symptom  being  epigastric  pain  and  tenderness, 
with  sickness  and  vomiting. 
24 


370       The  Pancreas:  Its  Surgery  and  Pathology 

Auche  has  reported  two  cases  of  pancreatitis  compH- 
cating  mumps. 

The  first  was  in  a  lad,  aged  twelve  years,  who  woke  dur- 
ing the  third  night  of  his  illness  complaining  of  pain  in 
the  epigastrium  of  a  continuous  nature,  with  exacerba- 
tions ;  in  half  an  hour  vomiting  occurred,  at  first  of  food, 
later  of  bile.  The  pain  was  confined  to  the  epigastrium, 
midway  between  the  umbilicus  and  xiphoid  cartilage, 
extending  as  far  as  the  left  costal  arch.  Owing  to  the 
tenderness  it  was  impossible  to  ascertain  if  there  was  any 
intra-abdominal  swelling.  During  the  ensuing  day  the 
pain  was  slightly  less,  the  exacerbations  were  less  frequent. 
Vomiting  occurred  four  or  five  times,  but  only  on  taking 
fluids.  The  bowels  acted  once;  the  motion  looked  as 
if  it  did  not  contain  fat.  Next  day,  the  fifth  since  the 
parotid  glands  were  swollen,  the  pain  was  still  less,  and 
less  frequent,  but  it  was  sufficiently  severe  to  prevent  deep 
palpation;  a  motion  passed  was  normal,  as  was  also 
the  urine.  Bilious  vomiting  continued.  Next  day,  the 
third  since  the  onset  of  abdominal  symptoms,  vomiting 
ceased,  and  liquid  food  was  well  borne.  On  the  fourth 
day  no  swelling  could  be  felt  on  deep  palpation.  The 
temperature  had  fallen  from  38.9°  C.  to  36.8°  C.  On 
the  fifth  day  the  patient  seemed  perfectly  recovered. 

The  second  case  was  a  boy,  aged  nine  years.  On  the 
fifth  day  of  an  attack  of  mumps,  suddenly  epigastric 
pain  and  vomiting  supervened.  Next  day  pain  and 
vomiting  continued.  When  these  symptoms  had  lasted 
three  days  the  patient  was  seen  for  the  first  time;  the 
pain  was  limited  to  the  left  side  of  the  epigastrium,  vom- 
iting had'  occurred  once  during  the  day,  the  liver  could 
be  felt  below  the  costal  arch.  Calomel  was  ordered. 
The  patient  was  only  seen  once. 

A  similar  case,  also  in  a  boy,  has  been  described  by 
Jacob.  In  this  instance  pain  in  the  abdomen  was  com- 
plained of  on  the  fourth  day  of  the  disease,  and  on  examin- 
ation a  tender  swelling  was  found  in  the  epigastrium. 
The  first  case  in  which  a  post-mortem  examination  had 
been  made  was  described  by  Lemoine  and  Lapasset  in 

1905- 


Inflammatory  Affections  of  the  Pancreas        371 

In  this  case  a  soldier,  a  native  of  Algiers,  aged  nineteen 
years,  was  admitted  into  hospital  on  OctoVjer  2,  1902, 
suffering  from  mumps.  The  only  previous  illness  was 
malarial  fever.  The  case  ran  a  benign  course,  the  tem- 
perature not  rising  above  100.2°  F.  and  becoming  nor- 
mal on  the  fifth  day.  On  the  eighth  day  the  illness 
appeared  to  have  terminated,  but  on  the  evening  of  the 
tenth  day  there  was  a  rigor  with  a  rise  of  temperature  to 
103.8°  and  pain  and  swelling  in  the  right  testicle.  The 
orchitis  rapidly  subsided,  the  temperature  became  nor- 
mal on  the  fourteenth  day,  and  the  patient  was  again 
pronounced  convalescent,  but  when  visited  on  the  morn- 
ing of  the  fifteenth  day  he  complained  that  he  had  not 
slept  and  that  he  vomited  several  times  during  the  night. 
Although  the  temperature  was  normal  he  appeared  to  be 
prostrated.  The  conjunctivae  showed  a  slightly  icteric 
tinge.  The  upper  abdomen  was  tender,  especially  in  the 
epigastrium  and  the  region  of  the  gall-bladder.  Here 
the  patient  had  a  feeling  of  weight.  The  spleen  was 
enlarged  and  tender.  The  pulse  was  slow  (52)  and  the 
axillary  temperature  was  97.3°.  An  aperient  was  given, 
but  it  was  vomited  and  produced  no  action  of  the  bowels. 
On  the  sixteenth  day  the  icteric  tint  involved  the  whole 
skin  and  the  discolouration  of  the  conjunctivae  was  more 
marked.  Vomiting  had  become  more  frequent  and  the 
intolerance  of  the  stomach  was  absolute,  all  liquids  being 
rejected.  The  hepatic  and  splenic  regions  were  very 
painful,  with  a  maximum  in  the  region  of  the  gall-bladder, 
which  organ  appeared  to  be  enlarged.  The  temperature 
and  pulse  remained  the  same.  An  injection  of  1000  grams 
of  saline  solution  was  ordered  in  order  to  provoke  ditiresis , 
as  the  kidneys  had  ceased  to  act  since  the  previous  day. 
In  the  evening  the  general  condition  seemed  to  have 
improved.  Vomiting  had  occurred  only  once  during  the 
day.  Eighty  grams  of  brownish-red  urine,  containing 
I  gram  of  albumin  per  litre  and  abundance  of  biliary  pig- 
ments, had  been  passed.  The  patient  continued  to  be 
very  prostrate  and  spoke  of  his  approaching  death.  In 
the  night  the  vomiting  recurred  and  was  uncontrollable. 
At  first  the  vomit  was  black,  then  it  gradually  became 
sanguineous.  There  was  also  constipation.  On  the 
seventeenth  day  the  haematemesis  was  incessant  and  the 


372       The  Pancreas:  Its  Surgery  and  Pathology 

patient  lost  consciousness.  The  pulse  rose  to  120  and 
the  temperature  to  101.5°  ^'^^  the  jaundice  increased  in 
depth.     Death  occurred  on  this  day. 

At  the  necropsy  all  the  tissues  had  an  icteric  tinge.  The 
liver  did  not  appear  to  be  enlarged,  but  it  was  much  con- 
gested ;  on  section  it  looked  like  a  "  cardiac  liver."  Some 
lobules  seemed  to  be  in  a  state  of  incipient  degeneration. 
The  gall-bladder  was  voluminous  and  oedematous.  This 
oedema  extended  as  far  as  the  beginning  of  the  common 
bile-duct,  where  an  enlarged  gland  pressed  on  the  latter 
and  appeared  mechanically  to  produce  the  oedema  of  the 
gall-bladder  and  the  icterus.  The  bile  in  the  gall-bladder 
was  brownish,  thick,  and  very  viscid.  The  stomach  con- 
tained black  fluid ;  its  mucous  membrane  was  spotted  with 
fine  ecchymoses  which  extended  as  far  as  the  first  part  of 
the  duodenum.  The  pancreas  was  greatly  enlarged,  oedem- 
atous, and  congested.  It  weighed  190  grams  and  was  of  a 
reddish-gray  colour.  All  the  region  around  the  pancreas, 
the  duodenum,  and  the  hilum  of  the  liver  contained  a 
large  number  of  swollen  lymphatic  glands.  The  spleen 
was  enlarged  and  weighed  1200  grams.  The  kidneys 
were  a  little  congested  and  the  capsules  were  adherent 
in  places.  Microscopic  examination  of  the  liver  showed 
proliferation  of  the  connective  tissue  surrounding  the 
biliary  canaliculi  and  a  number  of  nodules  composed  of 
embryonic  cells.  The  spleen  also  contained  nodules  of 
embryonic  cells  and  its  capsule  and  trabecule  were  thick- 
ened. In  the  kidneys  lesions  were  limited  to  the  convo- 
luted tubes,  the  cells  of  which  showed  signs  of  granulo- 
f  atty  degeneration  and  the  lumen  of  which  was  filled  with 
epithelial  debris.  The  cells  and  acini  of  the  pancreas  were 
abnoiTnally  large,  but  the  islands  of  Langerhans  were 
diminished,  being  compressed  by  the  turgescent  tubes. 
The  nuclei  of  the  pancreatic  cells  stained  badly  and  many 
of  them  were  vesicular. 

In  this  instance  the  delayed  onset  of  the  pancreatic 
symptoms  is  remarkable,  for  they  did  not  occur  until  the 
fifteenth  day,  whereas  in  most  instances  they  appear  to 
occur  about  the  third  or  fourth  of  the  illness.  In  addi- 
tion to  the  epigastric  pain,  which  was  the  principal  symp- 


Inflammatory  Affections  of  the  Pancreas        373 

torn  of  the  pancreatitis,  the  gall-bladder  was  tender  and 
the  spleen  was  tender  and  enlarged.  There  was  also 
grave  icterus  with  hasmatemesis,  prostration,  and  sub- 
normal temperature. 

An  outbreak  of  epidemic  parotitis,  accompanied  in  four 
cases  by  symptoms  suggestive  of  metastatic  pancreatitis, 
has  been  described  by  Dr.  Edgecombe,  of  Harrogate. 
The  urines  from  two  cases  in  this  epidemic  were  examined 
by  one  of  us.  In  the  first  no  striking  abnormality  was 
found  and  the  "pancreatic"  reaction  was  negative.  We 
are  informed  by  Dr.  Edgecombe  that  it  was  a  simple  case 
of  uncomplicated  parotitis.  In  the  second  the  urine  was 
acid  in  reaction,  specific  gravity  1.030,  no  albumin,  no 
sugar,  a  well-marked  reaction  for  acetone  and  for  diacetic 
acid  was  obtained,  there  was  a  fair  amount  of  indican, 
a  slight  pathological  excess  of  urobilin  was  present,  but 
no  bile-pigment  was  detected,  the  "pancreatic"  reaction 
(by  the  improved  or  C -method)  showed  many  fine  crys- 
tals, soluble  in  33  per  cent,  sulphuric  acid  in  ten  to  fifteen 
seconds.  The  history  of  this  case,  as  supplied  to  us  by 
Dr.  Edgecombe,  is  as  follows:  April  2 2d  a  moderate 
amount  of  parotid  swelhng,  with  no  constitutional  dis- 
turbance ;  April  2  5th  the  patient  was  delirious ;  April  2  7th 
there  was  severe  epigastric  pain  with  vomiting,  a  tem- 
perature of  100°  F.,  and  a  pulse  of  96;  April  28th  the 
vomiting  continued,  tenderness  and  swelling  in  the  epigas- 
trium were  detected;  April  29th  vomiting  less,  but  still 
pain  and  swelling  in  the  epigastrium,  temperature  102° 
F.,  pulse  105;  April  30th  pain  in  the  epigastrium  disap- 
peared, but  still  slight  swelling  and  tenderness,  tempera- 
ture and  pulse  normal.  It  will  be  noticed  that  in  these 
two  cases  the  results  of  the  "pancreatic"  reaction  coin- 
cided with  the  clinical  symptoms  and  course  of  the  disease. 

Among  the  blood  infections  have  to  be  mentioned 
"pyemia,"  which  presents  no  special  peculiarity  in  the 
pancreas,  and  "syphilis,"  which  may  affect  the  pancreas 


374      The  Pancreas:  Its  Surgery  and  Pathology 

either  avS  a  tertiary  affection  in  the  shape  of  gumma  or 
as  a  congenital  affection,  as  first  described  by  Birch- 
Hirschfeld.  It  produces  an  interstitial  pancreatitis  of 
the  interlobular  type  and  the  islands  of  Langerhans  are 
unaffected. 

That  the  spread  of  ulceration  inwards  from  the  stomach 
may  produce  an  indurative  pancreatitis,  or  even  suppu- 
ration in  the  pancreas,  can  be  readily  understood,  for 
the  ulcer  must  be  constantly  bathed  with  septic  matter 
and  the  eroding  action,  when  once  it  has  passed  through 
the  stomach  wall,  may  assume  great  activity.  The  effect 
of  the  spread  of  ulceration  is  also  well  exemplified  by  the 
case  (described  later)  of  pancreatic  abscess  apparently  due 
to  gastric  ulcer  bursting  into  the  stomach  and  setting  up 
acute  gastritis,  for  which  gastro-enterostomy  was  per- 
formed with  a  good  result. 

Whether  alcohol  can  act  directly  in  producing  cirrhosis 
is  a  matter  of  great  doubt,  the  probability  being  that  it 
sets  up  a  gastro-intestinal  catarrh  which  by  extension 
gives  rise  to  the  chronic  infective  process,  or  another 
explanation  may  be  in  the  fact  that  alcohol  causes  vascu- 
lar degeneration,  a  well-recognised  cause  of  chronic  inter- 
stitial pancreatitis. 

With  regard  to  cirrhosis,  the  most  chronic  form  of 
inflammation  of  the  pancreas,  which  is,  though  slow  in  its 
progress,  almost  necessarily  fatal  from  diabetes,  the  cause 
is  probably  a  long-continued  catarrh  setting  up  interlobu- 
lar and  interacinar  pancreatitis,  which  is  originally  due 
to  infection. 

Vascular  degeneration  is  ascribed  as  a  cause  of  chronic 
pancreatitis  in  old  or  in  prematurely  aged  persons. 

CATARRH  OF  THE  PANCREAS 
From  the  foregoing  remarks  on  the  etiology  of  inflam- 
mation of  the  pancreas  it  will  be  seen  that  catarrh  of  the 
pancreas  is  a  disease  as  well  worthy  of  recognition  as  is 


Inflammatory  Affections  of  the  Pancreas        375 

catarrhal  jaundice,  which  in  the  same  way  has  until 
recently  been  thought  to  be  always  dependent  on  catarrh 
of  the  bile-ducts.  It  is  held  that  biliary  catarrh  is  known 
to  exist,  as  it  can  be  so  readily  recognised  by  enlarge- 
ment of  the  liver  and  jaundice,  but  that  catarrhal  pan- 
creatitis is  beyond  recognition.  We  hope  to  be  able  to 
prove  that  these  views  regarding  diagnosis  will  need  revis- 
ing, for  catarrh  of  the  pancreas  can  also  be  usually  verified 
by  digestive  and  metabolic  signs,  and  by  swelling  of  the 
gland,  which  can,  in  some  cases,  .be  recognised  by  palpa- 
tion through  the  abdominal  wall,  but  in  others  only  by 
manipulation  of  the  pancreas  through  the  opened  abdo- 
men. Just  as  catarrh  of  the  bile-ducts  may,  and  usually 
does,  pass  off  if  the  cause  be  removed,  so  may  pancreatic 
catarrh  entirely  clear  up  under  appropriate  treatment. 
Should  the  cause  continue,  the  catarrh  will  become  chronic 
and  an  interstitial  pancreatitis  ensue  which  may  end  in 
cirrhosis  or  atrophy  of  the  gland— a  condition  which  prob- 
ably always  has  a  fatal  termination  from  diabetes. 

It  will  be  seen  that  chronic  interstitial  pancreatitis 
is  in  many  cases  simply  a  sequence  of  pancreatic  catarrh, 
and  as  the  latter  is  curable  by  appropriate  treatment, 
and  the  former,  when  well  advanced,  is  only  capable  of 
relief  and  probably  not  of  complete  cure,  it  is  of  the  ut- 
most importance  that  we  should  recognise  catarrh  of  the 
pancreatic  ducts  at  an  early  stage,  and  if  in  a  short  time 
it  fails  to  yield  to  medical  treatment,  that  we  should  per- 
form an  exploratory  operation  with  a  view  to  remove 
the  cause,  whether  that  be  gall-stones  or  some  other 
removable  condition ;  but  if  the  cause  be  not  discovered, 
or  if  when  found  it  proves  to  be  incapable  of  removal,  then 
drainage  of  the  bile-ducts,  either  by  cholecystenterostomy 
or  cholecystotomy,  will  nearly  always  aflord  relief:  (i) 
by  removing  the  infected  bile  and  thus  ridding  the  system 
of  poison  which  tends  to  deteriorate  the  blood;  and  (2) 
by  removing  the  pressure  of  pent-up  bile  from  the  pan- 


376       The  Pancreas:  Its  Surgery  and  Pathology 

creas,  thus  rcHeving  tension.  Still  another  beneficial 
effect  will  result  in  some  cases  where  the  obstruction  is 
at  the  papilla,  for  the  pancreatic  ducts  will  then  also  be 
drained  indirectly  through  the  bile-ducts.  In  certain 
cases  a  mere  manipulation  of  the  gland  without  drainage 
has  been  followed  by  recovery  and  apparently  by  cure. 
An  explanation  of  this  result  may  possibly  be  that  an 
obstruction  in  the  shape  of  concretions  or  adhesions  may 
have  been  inadvertently  removed  during  the  manipula- 
tion; but  in  one  case  thus  treated  without  drainage 
glycosuria  has  subsequently  developed,  which  possibly 
might  have  been  prevented  by  draining  the  ducts  in  the 
first  instance.  An  example  of  the  beneficial  effects  pro- 
duced by  draining  the  ducts  in  catarrhal  pancreatitis  is 
afforded  by  the  following  case : 

A  patient,  aged  thirty-eight,  after  being  subject  to 
indigestion  for  years  had  biliary  colic  in  July,  1899,  and 
passed  gall-stones,  which  were  found  in  the  motions. 
Subsequently  the  attacks  of  pain  were  frequent  and  se- 
vere, necessitating  the  use  of  morphia.  They  were  usually 
accompanied  by  icterus,  which,  though  slight,  probably 
never  quite  disappeared.  When  seen  on  November,  1903, 
he  had  lost  flesh  and  was  prevented  from  carrying  on  his 
professional  duties.  The  metabolic  and  digestive  signs 
of  pancreatic  catarrh  were  well  marked.  At  the  opera- 
tion on  November  23,  1903,  no  gall-stones  were  found, 
though  the  gall-bladder  was  thickened  and  adherent  to 
contiguous  organs.  The  pancreas  was  firmer  than  usual, 
though  not  very  much  swollen.  Cholecystotomy  led  to 
recovery,  though  the  drainage  of  the  bile-ducts  had  to  be 
continued  for  three  months.     The  patient  is  now  well. 

In  this  case  the  pancreatic  catarrh  had  evidently  been 
set  up  by  the  passage  of  gall-stones  through  the  common 
duct.  The  pancreatitis  had,  however,  persisted,  and 
was  not  only  keeping  up  painful  symptoms,  but  leading 
to  obstruction  of  the  bile-ducts  and  to  interference  with 
nutrition.     This  case  would  formerly  have   been  called 


Inflammatory  Affections  of  the  Pancreas        377 

catarrhal  jaundice,  whereas  it  was  really  due  to  catarrhal 
pancreatitis,  as  proved  by  the  digestive  and  metabolic 
signs  and  later  by  operation. 

Just  as  post-mortem  evidence  is  not  easy  to  obtain  in 
simple  catarrh  of  the  liver,  so  it  is  reasonable  to  antici- 
pate that  pathologists  will  rarely  find  gross  lesions  of 
the  pancreas,  even  if  opportunity  for  a  post-mortem 
examination  occurs,  in  cases  of  catarrhal  pancreatitis. 
The  micro-photographs  in  Fig.   121  are  from  a  case  of 


Fig.  121. — a,  Catarrh  of  the  pancreas  during  incipient  stage  of  inter- 
stitial pancreatitis  (X  30) ;  h,  a.  portion  of  the  same  more  highly  mag- 
nified, showing  the  round-celled  infiltration  (X  190)- 


early  interstitial  pancreatitis  where  death  occurred  in 
an  aged  patient  twelve  hours  after  operation,  appar- 
ently from  a  cerebral  attack  that  came  on  during  anaesthe- 
sia. A  gall-stone  was  impacted  in  the  common  duct  and 
pressed  on  the  pancreatic  duct,  the  pancreas  being  found 
swollen  at  the  time  of  operation.  There  was  a  well-marked 
pancreatic  urinary  reaction  before  operation.  At  the 
necropsy  no  gross  lesion  of  the  pancreas  could  be  seen, 
but  microscopically  there  were  small-celled  infiltration, 


378       The  Pancreas:  Its  Surgery  and  Pathology 

congested  vessels,  in  fact,  an  incipient  interstitial  pancrea- 
titis, and  it  is  probable  that  careful  investigation  would 
demonstrate  similar  microscopic  lesions  in  cases  where  no 
gross  changes  are  manifest. 

It  is  not  necessary  to  consider  separately  the  sympto- 
matology of  acute  and  chronic  catarrh  of  the  pancreas, 
as  the  symptoms  and  signs,  though  less  in  degree,  are 
practically  the  same  as  those  of  chronic  pancreatitis, 
under  which  subject  they  will  be' fully  dealt  with. 


SUPPURATIVE  CATARRH 

This  disease  bears  the  same  relation  to  simple  pan- 
creatic catarrh  that  simple  catarrhal  jaundice  does  to 

suppurative  chol- 
angitis and,  like 
the  latter,  it  is  an 
extremely  serious 
and  frequently  a 
fatal  disease.  In 
all  the  cases  we 
have  seen  gall- 
stones have  been 
the  cause,  but 
why  some  patients 
should  have  sim- 
ple catarrh  ending 
in  chronic  inter- 
stitial pancreatitis 
and  others  should 
at  once  develop  an 
acute  suppuration 
of  the  pancreatic 
duct  it  is  difficult  to  say,  unless  one  may  surmise  that  in 
the  latter  class  the  infection  may  be  of  a  more  virulent 
character  and  the  patient's  tissues  less  able  to  withstand 
the  attack.     The  disease  tends  towards  death  from  septi- 


Fig.  122. — Camera  lucida  drawing  of 
suppurative  catarrh  of  the  pancreatic  ducts : 
I,  Exudation  and  cells,  2,  duct;  3,  acini; 
4,  pus;  5,  detached  epithelium  (A.  J.  Chal- 
mers, Journ.  of  Ceylon  Branch  of  Brit.  Med. 
Assoc,  vi,  part  2,  1904). 


Inflammatory  Affections  of  the  Pancreas        379 

csemia,  or  if  the  process  be  less  acute,  or  the  vital  powers 
more  resistant,  it  may  possibly  end  in  a  localised  abscess. 
Suppurative  catarrh  of  the  pancreatic  ducts  is  generally, 
if  not  always,  combined  with  suppurative  cholangitis. 
The  following  four  cases  illustrate  the  serious  nature  of 
the  disease,  but  show  that  it  is  not  necessarily  hopeless  if 
treated  early. 

If  the  suppurative  catarrh  be  diffuse  and  involve  the 
ducts  throughout  the  liver  and  pancreas,  the  associated 
septicaemia  is  very  serious,  as  the  following  case,  seen 
with  Dr.  Hector  Mackenzie,  proves: 

Mr.  W ,  aged  sixty-five  years,  seen  on  January 

4,  1904.  He  had  had  attacks  of  gall-stones  seven  years 
before  and  two  seizures  during  the  last  two  years,  both  of 
which  were  followed  by  jaundice.  His  present  illness 
started  on  November  23d  with  severe  pain,  followed  by 
jaundice.  On  December  20th  a  very  severe  attack  of 
colic  was  followed  by  more  intense  jaundice  and  enlarge- 
ment of  the  liver  with  irregular  temperature  and  ague-like 
attacks.  The  patient  had  had  albimiinuria  for  seven  or 
eight  years.  On  examination  there  was  tenderness  above 
and  to  the  right  of  the  umbilicus  and  he  had  severe  pain. 
A  specimen  of  the  urine  was  examined,  and  found  to  give 
a  marked  pancreatic  reaction,  and  to  contain  calcium 
oxalate  crystals.  On  opening  the  abdomen  on  January 
7th,  firm  adhesions  were  encountered,  and  on  detaching 
the  omentum,  phlegmonous  cholecystitis  was  discovered, 
with  gangrene  of  the  fundus  of  the  gall-bladder;  pus 
escaped  freely,  but  the  peritoneal  cavity  w^as  saved  from 
being  soiled  by  means  of  sponge  packing.  The  common 
duct  was  enormously  dilated  and  embraced  by  the  swollen 
pancreas,  but  no  gall-stones  could  be  felt.  On  opening 
the  common  duct  a  large  quantity  of  pus  and  bile  escaped. 
By  means  of  the  scoop  passed  into  the  common  duct 
and  the  fingers  passed  behind  the  pancreas  a  number  of 
'  gall-stones  were  extracted,  but  a  hardness  could  be  felt 
at  the  papilla  which  could  not  be  removed.  On  laying 
this  open  after  incising  the  duodenum,  a  gall-stone  was 
removed  from  the  ampulla  of  Vater,  and  pus  was  imme- 
diately seen  to  flow  from  the  duct  of  Wirsung.     The  duo- 


380       The  Pancreas:  Its  Surgery  and  Pathology 

denum  was  then  closed,  the  gangrenous  upper  part  of  the 
gall-bladder  was  removed,  and  the  common  duct  and 
gall-bladder  were  drained.  The  patient  bore  the  operation 
well,  and  from  that  time  onwards  had  no  more  fever,  but 
for  the  fortnight  during  which  he  lived  his  temperature 
was  persistently  subnormal.  He  had  no  peritoneal  symp- 
toms and  the  bowels  were  moved  freely  from  the  second 
day  onwards.  Calcium  chloride  had  been  given  before 
operation,  and  at  the  operation  he  lost  no  blood.  None 
was  given  subsequently  to  operation,  as  the  rectum  was 
intolerant  of  injections,  and  on  the  eighth  day  there  was 
rather  free  oozing  of  blood  from  the  drainage  track,  which 
had  to  be  treated  by  gauze  packing,  after  which  the  cal- 
cium chloride  was  resumed,  and  no  more  bleeding  occurred. 
On  the  eleventh  day  the  patient  became  somnolent  and 
declined  to  take  food.  From  this  time  he  got  gradually 
weaker,  and  died  comatose  on  the  fourteenth  day  in  a 
condition  almost  resembling  that  associated  with  acute 
atrophy  of  the  liver. 

If  the  suppurative  catarrh  takes  on  a  very  acute  form, 
the  development  of  abscess  in  the  liver  and  pancreas  may 
occur,  and  the  condition  become  one  of  pyaemia,  when  the 
chance  of  recovery  will  be  very  remote,  as  in  the  following 
case: 

The  patient,  a  woman,  aged  sixty-five  years,  seen  with 
Sir  William  Broadbent  and  Dr.  Bousfield,  was  suffering 
from  deep  jaundice,  suppurative  cholangitis,  pancreatitis, 
and  parotitis  of  pysemic  origin ;  rigors  with  a  temperature 
of  105°  occurring  daily,  or  even  twice  a  day,  the  acute 
symptoms  having  come  on  within  a  fortnight,  though 
there  had  been  a  history  of  gall-stones  for  years.  The 
common  and  hepatic  ducts  were  filled  with  gall-stones, 
which  were  removed  through  an  incision  in  the  common 
duct,  and  a  large  quantity  of  extremely  offensive  pus  and 
bile  was  evacuated.  At  the  same  time  the  right  parotid 
gland  (the  seat  of  inflammation)  was  incised.  The  bile 
was  examined  bacteriologically,  and  found  to  contain  the 
bacillus  coli  in  large  numbers ;  next  in  numbers  were  strep- 
tococci and  another  rather  fine  bacillus,  which  appeared 
to  grow  anaerobically  only,  and  there  was  a  fine  spore- 


Inflammatory  Affections  of  the  Pancreas        381 

bearing  organism,  probably  the  bacillus  putrificus  coli. 
The  urine  gave  a  well-marked  pancreatic  reaction.  The 
patient,  who  had  also  heart  disease  and  albuminuria, 
appeared  to  be  doing  well  for  twenty-four  hours,  when 
she  died  suddenly,  apparently  from  cardiac  thrombosis. 

If  the  suppurative  catarrh  assumes  a  subacute  form, 
it  may  end  in  a  simple  pancreatic  abscess,  which  can  be 
successfully  evacuated,  as  in  the  following  cases: 

Mrs.  P.,  aged  sixty-one,  gave  the  history  of  having  been 
subject  to  biUary  colic  for  three  or  four  years,  though 
there  had  been  no  jaundice  till  two  and  a  half  years  ago, 
since  which  time  the  attacks  of  pain  had  always  been 
accompanied  by  rigors  and  by  deepening  of  the  jaundice. 
Within  a  short  time  of  being  first  seen,  the  symptoms  had 
become  aggravated,  and  the  loss  of  flesh  had  become 
extreme.  The  patient  was  so  ill  that  the  question  of  can- 
cer of  the  pancreas  was  raised,  but  the  pancreatic  reaction 
in  the  urine  and  a  chemical  examination  of  the  faeces  defi- 
nitely pointed  to  inflammation  and  not  to  growth.  At 
the  operation  the  pancreatic  portion  of  the  common  duct 
was  packed  with  large  gall-stones  and  the  head  of  the 
pancreas  was  markedly  swollen.  On  passing  the  scoop 
through  the  opening  in  the  common  duct,  a  stone  the  size 
of  a  cherry  was  extracted  from  the  pancreatic  portion 
of  the  duct,  it  being  covered  with  offensive  pus.  This 
had  apparently  lodged  in  a  cavity  in  the  head  of  the  pan- 
creas. A  profuse  discharge  of  bile  and  offensive  pancrea- 
tic fluid  with  pus  continued  to  pass  for  a  week,  after  which 
.  the  discharge  became  gradually  less.  She  made  a  good 
recovery,  and  was  well  two  years  later. 

In  general  subacute  pancreatitis,  starting  as  suppura- 
tive catarrh  with  the  formation  of  a  locaHzed  abscess,  the 
pancreas  may  be  so  damaged  that  after  the  abscess  has 
been  cured  by  drainage,  the  extensive  interstitial  pan- 
creatitis may  ultimately  lead  to  the  death  of  the  patient 
at  a  longer  or  shorter  interval,  as  in  the  following  cases : 

Mr.  H.,  aged  forty,  had  suffered  from  continuous  fever, 
with  exacerbations  associated  with  rigors,  that  recurred 


382       The  Pancreas:  Its  Surgery  and  Pathology 


almost  daily.  He  gave  the  history  of  failing  health  for 
nine  months,  and  of  having  had  gall-stone  attacks  much 
longer,  but  the  acute  symptoms  associated  with  jaundice 
had  only  been  present  for  a  fortnight.  The  pancreatic 
reaction  was  found  in  the  urine.  At  the  operation,  on 
October  11,  1900,  he  was  far  too  ill  to  bear  a  prolonged 
search,  and  as  the  adhesions  were  very  firm,  it  was  felt 
desirable  only  to  drain  the  bile-ducts  through  the  gall- 
bladder, though  a  marked  swelling  of  the  pancreas  made 
it  appear  probable  that  an  abscess  might  be  present, 
A  large  quantity  -of  muco-pus  drained  from  the  gall-blad- 
der and  a  number  of 
gall-stones  were  re- 
moved. The  abscess 
of  the  pancreas  dis- 
charged subsequently 
through  the  drainage- 
tube,  after  which  the 
pancreatic  swelling 
subsided.  The  patient 
made  a  slow  though 
steady  recovery,  and 
returned  home  early 
in  December.  Though 
he  was  able  to  get  out 
and  to  take  food,  he 
never  fully  regained 
his  strength,  and  died 
in  February  of  the  fol- 
lowing year.  At  the 
necropsy  the  pancreas  was  found  to  be  much  enlarged 
and  to  be  the  seat  of  interstitial  pancreatitis.  The  cavity 
where  the  abscess  had  been  was  occupied  by  a  little  pulpy 
material,  but  no  further  collection  of  pus  was  formed, 
nor  were  any  gall-stones  discovered  in  the  bile-ducts.  A 
microscopic  examination  of  the  pancreas  showed  advanced 
interstitial  pancreatitis. 

The  preceding  cases  are  most  instructive  in  that  they 
illustrate  one  of  the  dangers  of  cholelithiasis,  which  might 
he  avoided  by  appropriate  treatment  at  an  earlier  stage, 
for  the  removal  of  gall-stones  before  the  onset  of  deep 


'^' 


Fig.  123. — Microphotograph  of  the 
pancreas  from  a  case  of  chronic  sup- 
purative pancreatitis  (X  40). 


Inflammatory  Affections  of  the  Pancreas        383 

jaundice  and  infection  of  the  bile  and  pancreatic  ducts 
is  with  due  care  and  in  skilful  hands  almost  devoid  of 
danger.  So  far  as  we  know,  these  conditions  were  first 
described  in  the  Hunterian  Lectures  for  1904  as  separate 
a.nd  distinct  diseases.  The  reasons  given  and  the  cases 
related  show  a  justification  for  separating  catarrhal  inflam- 
mation about  to  be  described.  Simple  catarrh  of  the 
pancreas  can  be  treated  most  successfully  if  taken  in  time, 
but,  as  will  have  been  noticed,  suppurative  catarrhal  pan- 
creatitis is  quite  as  serious  as  acute  phlegmonous  pancrea- 
titis, and  unless  treated  surgically  must  be  almost  neces- 
sarily fatal. 

Literature 

Auche:   Journ.  de  Med.  de  Bordeaux,  Oct.  29,  1905. 

Baillie:   "Morbid  Anatomy,"  1799. 

Birch-Hirschfeld:  Arch.  d.  Heilkunde,  1875,  xvi,  174. 

Edgecombe:  Brit.  Med.  Journ.,  Feb.  16,  1907. 

Fitz:  Med.  Record,  1889,  xxxv,  197. 

Guinard:    Brit.  Med.  Journ.,  March  16,  1907,  p.  656. 

Halsted:   Quoted  by  Opie,  "Diseases  of  the  Pancreas,"  1903. 

Helly:  Arch.  f.  mik.  Anat.,  Bd.  Hi,  p.  773. 

Jacob:    Brit.  Med.  Journ.,  June  23,  1900,  p.  1532. 

Lemoine  and  Lapasset:  Bull,  de  la  Soc.  Med.  des  Hopit.,  July  7,  1905. 

Mayo:   Address  to  the  Amer.  Surg.  Associat. 

Opie:   "Diseases  of  the  Pancreas,"  1903. 

Percivai:  Tr.  Assoc.  King's  Coll.  Ireland,  18 18  p.  128. 

Portal:   "Anat.  Med.,"  1804,  p.  353. 

Robson,  Mayo:    Hunterian  Lectures,  Lancet,  March  19,  26,  April  2, 

1904. 
Simoni:   Bull,  de  la  Soc.  Med.  des  Hopit.,  July  30,  1903. 
Smith:  Lancet,  July  28,  1901. 
Testut:   "Traite  de  Anat.  Humaine,"  viii,  1894. 
Tulpius:   "Observat.  Med.,"  1672,  p.  328. 


CHAPTER  XV 

ACUTE  PANCREATITIS  AND  SUBACUTE 
PANCREATITIS 

ACUTE   PANCREATITIS 

Symptoms. — Acute  pancreatitis  is  usually  ushered  in-  by 
a  sudden  pain  in  the  superior  abdominal  region,  accom- 
panied by  faintness  or  collapse,  and  followed,  sooner  or 
later,  by  vomiting.  There  is  usually  some  epigastric 
swelling  with  tenderness  from  the  first,  and  if  the  warm 
flat  hand  be  placed  over  the  epigastrium,  and  retained 
there  without  movement  for  a  time,  it  will  be  found  that 
the  swelling  is  diffuse  and  not  simply  dependent  on  a  dis- 
tended stomach  or  colon,  though  later,  when  peritonitis 
is  established,  the  hollow  viscera  become  inflated.  It  is 
almost  constantly  accompanied  by  constipation,  so  that 
it  is  quite  usual  for  these  cases  to  be  mistaken  at  first  for 
intestinal  obstruction.  The  obstruction,  however,  is  not 
absolute,  flatus  passes,  and  a  large  enema  may  secure  an 
evacuation ;  if  the  patient  survives  for  several  days  diar- 
rhoea may  supervene.  The  pain  may  be  so  severe  as  to 
produce  syncope  or  collapse,  and  though  the  pain  does 
not  quite  pass  away,  it  has  a  tendency  to  be  paroxysmal 
and  to  be  increased  by  movement;  it  is  associated  with 
well-marked  tenderness  just  above  the  umbilicus  and 
between  it  and  the  ensiform  cartilage.  The  pain  is  soon 
folowed  by  distension  in  the  superior  abdominal  region, 
which  may  become  general,  and  usually  does  so  in  the 
later  stages,  and  by  vomiting,  first  of  food,  then  of  bile, 
and  soon  of  black,  altered  blood.  The  vomiting  may  be 
severe  and  each  attack  of  sickness  aggravates  the  pain. 
Rarely   vomiting  may   not   be   a   prominent   symptom. 

384 


Acute  Pancreatitis  and  Subacute  Pancreatitis    385 

Slight  jaundice  from  associated  catarrh  of  the  bile-ducts 
and  pressure  is  usually  present  and  deepens  the  longer  the 
patient  survives.  As  the  impaction  of  a  gall-stone  in  the 
ampulla  of  Vater  is  probably  one  of  the  most  frequent 
causes,  the  jaundice  may  become  intense,  from  a  complete 
stoppage  of  the  passage  of  bile  into  the  duodenum.  The 
aspect  is  anxious  and  the  face  is  pinched,  resembling  the 
facies  of  peritonitis,  which,  in  fact,  is  usually  present. 
The  pulse,  which  is  rapid  and  small,  is  a  better  guide  than 
the  temperature,  which  may  be  normal,  subnormal,  irreg- 
ular, or  high.  In  the  ultra-acute  cases  the  temperature 
is  usually  subnormal,  but  in  the  cases  that  survive  for 
several  days  the  temperature  becomes  irregular  and  may 
be  excessive.  Delirium  comes  on  in  the  later  stages. 
The  distension  and  tenderness  may  prevent  an  exact 
examination  of  the  pancreas,  which  would  otherwise 
be  found  enlarged.  Death  usually  supervenes  from  the 
second  to  the  fifth  day  from  collapse,  probably  due  to 
absorption  of  virulent  matter,  though  in  the  less  acute 
cases  life  may  be  more  prolonged  and  recovery  may  possi- 
bly occur,  as  in  cases  related  below,  proved  by  laparotomy 
and  the  discovery  of  extensive  fat  necrosis,  and  by  others 
reported  elsewhere.  Acute  pancreatitis  thus  takes  on 
the  form  of  acute  peritonitis  starting  in  the  superior 
abdominal  region.  If  life  be  prolonged,  the  condition 
may  become  one  of  subacute  pancreatitis,  the  onset  in 
such  a  case  being  usually  less  grave,  though  often  equally 
sudden.  It  is  even  possible  for  the  trouble  to  resolve, 
apparently  completely,  and  then  for  a  relapse  to  occur, 
this  sequence  being  repeated  on  several  occasions. 

The  preceding  description  refers  to  acute  pancreatitis 
generally  and  applies  to  the  hsemorrhagic,  gangrenous,  or 
suppurative  varieties,  which  are  phases  of  the  same  infec- 
tive conditions,  though  the  morbid  appearances  differ 
so  much.  In  gangrenous  pancreatitis  the  organ  is  dry 
and  dark  or  even  black,  and  there  can  be  little  doubt,  as 
25 


386       The  Pancreas:  Its  Surgery  and  Pathology 

Opie  has  remarked,  that  this  condition  represents  a  late 
stage  of  the  hsemorrhagic  form.  What  has  been  pre- 
viously said  concerning  pancreatic  haemorrhage  will  show 
that  neither  clinicians  nor  pathologists  are  agreed  on 
this  subject,  some  believing  that  inflammation  precedes 
the  hsemorrhage, — among  these  being  Fitz,  who  designates 
the  disease  "  hsemorrhagic  pancreatitis," — others  holding 
that  the  haemorrhage  precedes  inflammation,  which  is,  in 
fact,  caused  by  bacterial  infection  of  the  haemorrhagic 
effusion.  It  is  probable  that  both  views  may  be  correct 
in  different  cases,  for  although  a  primary  pancreatitis 
may  be  accompanied  by  haemorrhage,  yet  this  origin  is 
not  the  only  one,  and  there  are  many  cases  in  which 
haemorrhage  precedes  and,  in  fact,  is  the  cause  of,  inflam- 
mation ;  first,  owing  to  the  great  tendency  of  the  gland  to 
disruption  because  of  its  soft  structure  when  haemorrhage 
does  occur;  secondly,  owing  to  the  setting  free  of  the 
pancreatic  secretion  which  decomposes  and  digests  the 
damaged  tissues;  thirdly,  owing  to  the  communication 
of  the  gland  with  the  intestine,  rendering  the  access  of 
putrefactive  organisms  likely;  and,  fourthly,  owing  to 
the  great  tendency  of  the  damaged  gland  and  the  effusion 
to  become  decomposed  as  soon  as  organisms  gain  access. 
From  its  proximity  to  the  peritoneum,  acute  peritonitis 
rapidly  follows  acute  pancreatitis.  These  two  varieties 
of  haemorrhagic  pancreatitis  may  at  times  be  clinically 
differentiated,  the  ultra-acute,  with  a  violent  and  sudden 
onset,  accompanied  by  collapse  and  ending  fatally  with 
extreme  rapidity,  being  for  the  most  part  the  ones  where 
the  hemorrhage  precedes  the  inflammation,  and  the 
somewhat  less  though  still  acute  cases,  where  the  onset  is 
more  gradual,  where  the  symptoms  are  not  ushered  in  by 
collapse,  and  where  resolution  and  relapse  are  liable  to 
occur,  being  the  ones  where  the  inflammation  precedes 
the  haemorrhage.  The  varieties  in  which  the  inflamma- 
tion precedes  the  haemorrhage  may  in  the  severer  forms 


Fig.  124. — Pancreas  and  adjacent  tissues  from  a  case  of  acute 
hemorrhagic  pancreatitis  with  fat  necrosis  (St.  Bartholomew's  Hosp. 
Museum). 


Acute  Pancreatitis  and  Subacute  Pancreatitis    387 

approach  the  subacute  varieties  of  pancreatitis.  These 
views  simplify  the  subject  and  place  the  disease  of  haemor- 
rhagic  pancreatitis  in  a  line  with  other  well-known  inflam- 
mations. The  coloured  plate  (Fig.  124)  shows  a  striking 
specimen  of  acute  haemorrhagic  pancreatitis  with  fat 
necrosis,  preserved  by  the  Keiserling  process,  in  St.  Bar- 
tholomew's Hospital  Museum. 

The  specimen  represented  in  Fig.  125,  copied  from 
Nothnagel,  is  in  the  Warren  Anatomical  Museum  of  Har- 
vard   Medical    School.     It    exemplifies    a    case    of   true 


0» 


Fig.  125. — Acute  hsemorrhagic  pancreatitis  (Oser). 

hsemorrhagic  pancreatitis,  of  four  days'  duration,  in 
which  the  inflammation  was  the  cause  of  the  hcemorrhage. 

A  well-marked  example  of  haemorrhagic  pancreatitis 
from  the  museum  of  the  Leeds  Medical  School,  which  was 
under  the  care  of  Mr.  B.  G.  A.  Moynihan  and  was  depen- 
dent on  gall-stones,  is  seen  in  Fig.  126. 

A  specimen  in  St,  George's  Hospital  Museum  (204  A) 
is  a  good  example  of  haemorrhagic  or  necrotising  pancrea- 
titis (Fig.  127).  The  case  was  reported  in  the  "Lancet" 
of  October  19,  1901,  p.  1041, 

Etiology. — In  many  cases  of  acute  pancreatitis  the 
etiology  is  obscure,  for  although  the  disease  is  capable  of 


388       The  Pancreas:  Its  Surgery  and  Pathology 

being  produced  artificially  by  injection  of  bile,  bile  salts, 
and  other  substances  into  the  main  pancreatic  duct,  yet 


( 


Fig.  126. — Specimens  from  a  case  of  acute  pancreatitis  (Leeds 
Museum,  E  E  200):  o,  Gall-bladder  containing  stone;  b,  slough  of  the 
pancreas;   c,  piece  of  omental  fat,  showing  fat  necrosis. 


in  only  a  few  cases  has  it  been  produced  in  a  similar  way 
by  diseases  in  the  human  subject. 

In  some  cases  septic  influences  have  been  causative  and 


Acute  Pancreatitis  and  Subacute  Pancreatitis    389 


in  others  blood  disorders,  but  in  a  considerable  number 
of  reported  cases  gall-stones  either  directly  or  indirectly 
have  been  instrumental  in  setting  up  the  disease. 

If  a  small  gall-stone  happens  to  descend  into  an  unusu- 
ally large  diverticulum  of  Vater  and  to  lodge  there,  it  will 
make  a  through  channel  from  the  common  bile-duct  into 
the  pancreatic  duct,  and  so  set  up  acute  pancreatitis, 
the  infected  bile  being  forced  direct  into  the  pancreatic 
duct,  as  in  Dr.  Halsted's  case, 
reported  in  O pie's  work  on  the 
pancreas. 

"L.  F.,  male,  aged  forty-seven 
years,  was  admitted  to  the  Johns 
Hopkins  Hospital  complaining  of 
abdominal  pain  and  fever.  He 
had  suifered  with  somewhat  fre- 
quent attacks  of  indigestion,  char- 
acterised by  pain  after  eating,  dis- 
tension, and  rarely  nausea  and 
vomiting,  but  otherwise  had  en- 
joyed good  health.  Six  months 
before  his  present  illness  he  had 
had  an  attack  of  jaundice,  lasting 
about  three  weeks,  and  accom- 
panied by  abdominal  pain.  The 
present  illness  began  eighteen 
days  before  admission,  when  he 
was  suddenly  seized  with  violent 
nausea  and  vomiting,  accompan- 
ied by  intense  cramp-like  pain  in 

the  abdomen.  The  vomiting  continued  during  the  first 
night,  and  had  since  only  occasionally  recurred.  The  ab- 
dominal pain,  which  was  not  localised,  remained  severe 
during  four  or  five  days,  and  at  times  there  were  symptoms 
of  collapse.  The  abdomen  was  distended  and  the  bowels 
were  constipated  until  the  fifth  day,  when,  with  the  aid  of 
a  purgative,  movement  occurred.  The  stool  was  normal 
in  colour.  On  the  third  day  elevation  of  temperature  to 
101.5°  F.  was  noted.  About  the  seventh  day  tenderness 
and  slight  swelling  were  noticed  in  the  right  hypochon- 


Fig.  127 . — Acute  haem- 
orrhagic  pancreatitis  and 
necrosis  of  the  pancreas 
(St.  George's  Hosp.  Mu- 
seum, 204  A). 


390       The  Pancreas:  Its  Surgery  and  Pathology 

drium.  Since  this  time  the  patient  had  an  irregular  tem- 
perature (ioo°  to  103°  F.),  with  several  chills.  After 
the  first  few  days  the  abdominal  pain  and  tenderness  were 
riot  severe,  but  the  distension  of  the  abdomen  gradually 
increased.     Jaundice  was  not  noticed. 

"  Physical  examination:  The  conjunctivae  have  a  slight 
yellow  cast.  On  inspection  of  the  abdomen  a  distinct 
prominence  is  found  to  occupy  the  right  hypochondriac 
and  right  half  of  the  epigastric  region,  extending  into  the 
upper  half  of  the  umbilical  region.  Its  lower  margin, 
which  descends  on  inspiration,  is  felt  in  the  middle  line 
at  the  level  of  the  umbilicus.  Its  right  border  cannot  be 
sharply  defined,  but  in  the  median  line  the  fingers  can  be 
pressed  in  above  it.  Over  the  resistant  mass  there  is 
dull  tympany.  The  leucocytes  number  1800.  The  urine 
is  clear,  its  reaction  is  acid,  and  specific  gravity  1.017. 
There  is  no  reduction  of  Fehling's  solution.  A  trace  of 
albumin  is  present.  On  the  second  day  after  admission 
a  stool  passed  was  of  a  golden  yellow  colour.  On  the 
third  day  the  leucocytes  numbered  19,500,  and  the  tem- 
perature varied  from  99.2°  to  101.8°  F.  During  the 
night  the  patient  was  irrational  at  times.  The  tempera- 
ture rose  gradually,  reaching  a  maximum  of  104°  F.  A 
liquid  stool  of  ochre-yellow  colour  was  passed.  The 
urine  had  a  specific  gravity  of  1.020  and  no  reaction  for 
sugar  was  obtained.  A  diagnosis  of  suppurative  pancrea- 
titis was  made  and  an  operation  for  its  relief  was  performed 
under  cocaine  anaesthesia.  A  linear  longitudinal  incision 
was  made  below  the  costal  margin  within  the  right  mam- 
millary  line.  After  incising  the  great  omentum  between 
the  stomach  and  transverse  colon,  an  abscess  cavity  was 
entered.  Grumous,  purulent  fluid,  containing  necrotic 
particles,  was  evacuated.  A  rubber  drainage-tube, 
packed  about  with  gauze,  was  inserted  into  the  wound. 
After  operation  the  pulse  remained  weak,  and  death 
followed  at  the  end  of  about  four  hours.  The  duration 
of  the  fatal  illness  was  twenty-one  days. 

''Autopsy:  Performed  three  hours  after  death.  The 
body  is  that  of  a  large-framed,  muscular  man,  with  abun- 
dant subcutaneous  fat.  The  omentum,  which  contains 
a  large  quantity  of  fat,  is  thickly  studded  with  conspicu- 
ous opaque  white  areas,  usually  round,  and  about  3  mm. 


Acute  Pancreatitis  and  Subacute  Pancreatitis    391 

in  diameter.  Similar  opaque  white  areas  are  present  in 
the  fat  of  the  mesentery,  in  the  subperitoneal  fat  of  the 
abdominal  wall,  over  the  bladder,  over  the  kidneys,  and 
about  the  colon.  The  drainage-tube  inserted  into  the 
abdominal  wound  passes  through  a  small  incision  in  the 
great  omentum  and  enters  an  immense  abscess  cavity; 
the  foramen  of  Winslow  is  closed.  The  walls  of  the  cavity 
are  very  irregular  and  ragged,  and  have  a  necrotic  appear- 
ance, in  general  opaque  and  grey,  occasionally  black. 
The  blackish-grey  appearance  extends  only  a  short  dis- 
tance below  the  surface,  and  where  the  wall  is  formed  of 
fat  gives  place  to  numerous  foci  of  opaque  white  colour. 
The  retroperitoneal  fat  in  front  of  the  left  kidney  and 
psoas  muscle  has  been  eroded,  and  an  extension  of  the 
cavity  passes  behind  the  jejunum  near  its  junction  with 
the  duodenum.  To  the  left  of  the  descending  part  of  the 
duodenum,  occupying  the  position  of  the  pancreas,  and 
projecting  forward  into  the  abscess  cavity,  is  a  great 
mass  of  black  material,  necrotic  in  appearance,  extending 
to  the  left  as  far  as  the  spleen.  The  material  is  reddish- 
brown  on  section,  somewhat  spongy  in  texture,  soft, 
dry,  and  friable.  The  cavity  contains  at  least  500  c.c. 
of  fluid,  reddish-grey  material,  in  which  are  fat  droplets 
and  black  necrotic  particles.  The  liver  is  flaccid  in  con- 
sistence. The  bile-ducts  are  slightly  dilated,  and  con- 
tain thin,  yellow  bile.  The  gall-bladder  is  bound  by 
numerous  adhesions  to  the  duodenum  and  stomach. 
Its  walls  are  thickened  and  it  is  much  distended,  con- 
taining viscid  yellow  bile  and  more  than  one  hundred 
brown,  faceted  calculi,  varying  in  diameter  from  0.5  to 
I  cm.  The  hepatic,  cystic,  and  common  ducts  are  much 
dilated.  On  opening  the  duodenum  a  stone  is  felt  below 
the  mucous  membrane,  situated  in  the  common  bile-duct 
near  its  termination.  It  is  7  mm.  in  diameter  and  resem- 
bles those  present  in  the  gall-bladder.  The  pancreatic 
duct  unites  with  the  common  bile-duct  at  a  point  7  mm. 
from  the  duodenal  orifice.  The  pancreatic  duct  is  not 
distended.  The  pancreas  occupies  the  posterior  wall  of 
the  abscess  cavity  of  the  lesser  peritoneum,  and  is  covered 
by  the  mass  of  reddish-brown,  friable  material,  changed 
coagulated  blood-clot,  above  described.  The  organ  is  of 
large  size,  and  the  glandular  tissue  is  in  great  part  firm. 


392       The  Pancreas:  Its  Surgery  and  Pathology 

yellowish- white,  and  well-preserved.  The  interstitial  tis- 
sue has  a  dull  reddish,  in  places  hsemorrhagic  appear- 
ance, and  contains  conspicuous  opaque  yellow  areas  of 
irregular  shape.  Where  the  anterior  surface  of  the  head 
and  body  is  in  contact  with  the  overlying  material  there 
is  a  superficial  zone  of  soft,  greyish,  necrotic  appearance. 
The  other  organs  present  no  noteworthy  alteration. 

''Histological  examination:  The  interstitial  tissue  of  the 
pancreas  is  much  increased  and  wide  bands  of  fibrous 
tissue  separate  groups  of  lobules.  Numerous  irregularly 
shaped  cells  filled  with  brownish-yellow  pigment  granules, 
which  give  the  prussian-blue  reaction  for  iron,  afford 
evidence  of  former  hemorrhage.  In  a  few  places  well- 
preserved  red  corpuscles  are  scattered  in  the  tissue.  Foci 
of  necrotic  fat  are  present.  Many  acini  are  widely  dilated ; 
their  cells  are  flat  and  the  lumen  is  much  distended,  con- 
taining products  of  secretion  and  occasionally  one  or. 
more  poly  nuclear  leucocytes.  In  an  area  corresponding 
to  the  superficial  zone  of  necrotic  appearance  before 
mentioned,  nuclei  no  longer  stain,  and  the  architecture 
of  the  glandular  tissue  is  only  obscurely  distinguished. 
A  thick  band  of  newly  formed  fibrous  tissue  containing 
an  occasional  acinus  or  duct  separates  the  necrotic 
parenchyma  from  that  which  is  still  intact.  The  mass 
covering  the  pancreas  is  found  to  consist  of  altered  blood ; 
upon  and  immediately  below  its  surface  are  numerous 
polynuclear  leucocytes. 

''Bacteriological  examination:  Cultures  from  the  blood 
contained  in  the  heart,  from  the  lungs,  and  from  the 
liver,  were  found  to  contain  the  bacillus  coli  communis, 
A  plate  culture  from  the  material  covering  the  pancreas, 
and  forming  part  of  the  abscess  wall,  contained  the 
bacillus  coli  communis,  the  bacillus  lactis  aerogenes, 
and  the  bacillus  proteus  vulgaris. 

"Anatomical  diagnosis:  Cholelithiasis;  calculus  lodged 
in  the  common  bile-duct  near  its  orifice;  slight  jaundice. 
Old  haemorrhage  within  and  about  the  pancreas,  with 
localised  necrosis  and  chronic  inflammation;  necrosis  of 
the  fat  of  the  pancreas,  greater  and  lesser  omentum, 
mesentery,  and  subperitoneal  fat  of  the  abdominal  wall; 
peri-pancreatic  abscess  limited  by  the  lesser  peritoneal 
cavity.     Laparotomy  wound." 


Acute  Pancreatitis  and  Subacute  Pancreatitis    393 

A  somewhat  similar  case  has  more  recently  been  re- 
ported by  Bunting  in  the  "Johns  Hopkins  Hospital 
Bulletin." 

"A  well-nourished  man,  aged  fifty-one,  was  subject  to 
attacks  of  epigastric  pain  with  some  constipation,  which 
were  usually  easily  relieved.  He  was  seized  with  intense 
epigastric  pain,  became  collapsed,  and  showed  considerable 
abdominal  distension.  Intestinal  obstruction  was  diag- 
nosed and  laparotomy  was  performed.  Some  peritoneal 
adhesions  were  freed  and  the  wound  was  closed.  There 
was  no  fat  necrosis  to  attract  attention  to  the  pancreas. 
Death  occurred  on  the  following  morning.  At  the  autopsy 
both  chronic  interstitial  and  acute  haemorrhagic  pan- 
creatitis were  found.  The  pancreas  was  large,  swollen, 
and  mottled  with  red  areas  of  haemorrhage  and  opaque 
areas  of  fat  necrosis.  The  gall-bladder  was  distended 
with  bile  and  the  bile-ducts  were  dilated  and  firm  to  the 
touch,  showing  that  there  was  obstruction  to  the  flow  of 
bile.  On  gentle  pressure  bile  did  not  escape  from  the 
papilla,  but  on  increased  pressure  there  was  a  sudden 
escape  of  bile,  carrying  before  it  a  small  yellowish-white 
mass,  which  was  unfortunately  lost.  In  the  bile-ducts  a 
stone  about  2  mm.  in  diameter  was  foiuid  in  the  apex  of 
the  ampulla  of  Vater,  close  to  the  orifice.  In  the  gall- 
bladder and  cystic  duct  were  about  400  soft,  light- 
coloured  cholesterin  stones,  varying  from  0.5  to  6  mm. 
in  diameter.  There  was  therefore  little  doubt  that  the 
escaped  mass  was  a  stone.  The  anatomical  relations  of 
the  ampulla  and  ducts  were  such  that  the  obstruction  set 
in  progress  the  mechanism  described  by  Opie,  and  re- 
sulted in  the  injection  of  bile  into  the  pancreatic  duct. 
This  duct  joined  the  common  bile-duct  1 1  mm.  from  the 
tip  of  the  papilla  and  was  dilated  and  bile-stained  for 
4  cm.  from  its  orifice.  The  common  duct  was  dilated  and 
somewhat  hypertrophied.  This,  in  connection  with  the 
induration  of  the  pancreas,  seemed  to  indicate  that  the 
previous  attacks  of  pain  were  due  to  the  passage  of  gall- 
stones, some  of  which  might  have  been  large  enough  to 
block  the  pancreatic  duct  in  transit  and  cause  the  chronic 
interstitial  pancreatitis." 


394       The  Pancreas:  Its  Surgery  and  Pathology 

But  the  anatomical  conditions  just  mentioned,  though 
evidently  potent,  are  certainly  not  necessary  for  the  pro- 
duction of  acute  pancreatitis.  Any  gall-stone  or  stones 
impacted  in  the  pancreatic  portion  of  the  duct,  or  even 
filling  the  ampulla  of  Vater,  may  produce  acute  pancrea- 
titis, as  in  a  case  under  the  care  of  Dr.  Fison,  of  Salisbury. 

"A  man,  aged  thirty-nine,  had  a  sharp  attack  of  diar- 
rhoea on  March  27,  1904,  having  been  previously  consti- 
pated. The  next  day,  about  one  and  one-half  hours  after 
dinner,  he  was  seized  with  severe  epigastric  pain  followed 
by  vomiting.  At  5  p.  m.  he  looked  anxious  and  ill,  and 
the  abdomen  was  tense  and  tympanitic,  but  there  was  no 
jaundice.  The  vomiting  persisted.  There  was  tenderness 
over  the  gall-bladder  and  to  a  less  degree  over  the  sto- 
mach, but  no  enlargement  of  the  liver  or  any  indication 
of  tumour.     Temperature,  98°;  pulse,  no. 

"  The  next  day  the  temperature  was  97°  and  pulse  120 ; 
the  vomiting  continuing,  morphia  was  given.  On  the 
30th  the  temperature  was  96.8°,  the  pulse  125,  small, 
weak,  and  thready,  respiration  36.  The  pain  was  easier. 
Urine  scanty  and  dark. 

''Operation  on  evening  of  the  30th,  fifty-four  hours 
after  first  attack  of  pain.  Very  extensive  fat  necrosis 
found  in  subcutaneous  tissues  and  in  omentum,  mesentery, 
etc.  Large  quantity  of  brown  inoffensive  fluid  in  perito- 
neum. Incision  made  into  tissues  around  pancreas 
through  mesocolon.  Gall-bladder  drained  through  an- 
other incision,  many  gall-stones  removed.  Free  drainage 
of  abdomen.  After  recovery  from  ansesthetic  the  vomit- 
ing persisted,  and  the  pulse  remained  absent  from  the 
wrist  up  to  death,  some  hours  later. 

"At  post-mortem  examination  a  pint  of  bloody  fluid 
in  peritoneal  cavity.  Base  of  mesocolon  filled  with 
friable  offensive  material,  blackish-brown  in  colour,  and 
here  and  there  streaked  with  pus.  Pancreas  much  swollen 
and  weighed  seventeen  ounces.  Haemorrhagic  infiltra- 
tion in  centre  of  body  and  another  in  tail;  consistency 
very  firm,  with  swelling  of  lobules.  In  the  cystic  duct 
were  three  gall-stones,  in  the  common  duct  four,  and  in 
the  hepatic  duct  four.     One  gall-stone  f  inch  in  length 


Acute  Pancreatitis  and  Subacute  Pancreatitis    395 

completely  filled  the  ampulla  of  Vater,  into  which  the 
duct  of  Wirsung  opened  one-third  of  an  inch  from  the 
papilla.     The  duct  of  Wirsung  did  not  contain  bile. 

"  Urine  sent  for  examination  by  Dr.  Cammidge  showed 
crystals  soluble  in  one-half  minute  by  the  'A'  reaction, 
and  a  few  crystals  by  the  'B'  reaction  soluble  in  the  same 
time. 

"The  following  is  Dr.  R.  Salisbury  Trevor's  report  of 
examination  of  the  pancreas : 

"  The  gland  is  enlarged  in  all  its  diameters,  the  margins 
being  rounded  off  and  producing  as  a  consequence  a 
sausage-shaped  contour.  In  the  head,  the  middle  of  the 
body,  and  the  tail  are  chocolate-coloured  areas,  which 
are  fairly  sharply  differentiated  from  the  surrounding 
parenchyma  in  which  the  normal  lobulation  is  visible. 
The  duct  of  Wirsung  is  not  bile-stained.  The  portion 
of  common  bile-duct  attached  to  the  head  of  the  gland 
appears  to  be  somewhat  dilated.  Around  the  gland, 
as  well  as  in  it,  are  numerous  typical  foci  of  fat  nec- 
rosis. 

"Microscopical  examination:  Sections  have  been 
prepared  from  the  head,  body,  and  tail,  in  most  instances 
to  include  the  chocolate-coloured  areas  as  well  as  ap- 
parently normal  parenchyma.  The  dark  coloured  areas 
are  due  to  necrosis  of  the  parenchyma  associated  with 
haemorrhage,  and  in  the  sections  from  the  head  and 
tail  are  demarcated  off  from  the  neighbouring  gland  acini 
by  well-marked  zones  of  inflamniatory  small-celled  in- 
filtration. In  the  tail  section  inflammatory  reaction  is 
absent,  the  necrosed  areas  merging  gradually  with  the 
unaffected  parenchyma.  In  the  necrosed  areas  the  gland 
parenchyma  is  only  barely  recognisable  by  a  faint  alveolar 
structure,  all  gland  elements  having  disappeared.  The 
whole  of  these  areas  stain  badly.  In  the  necrotic  por- 
tions the  smaller  blood-vessels  are  filled  with  more  or  less 
hyaline  thrombi.  Around  the  necrotic  areas  in  the  head 
and  body  is  a  deposit  of  old  blood-pigment,  and  the  ap- 
pearances rather  suggest  that  here  the  lesions  are  of 
older  date  than  those  in  the  tail.  Inflammation  is  most 
marked  in  sections  of  the  head.  The  remaining  gland 
parenchyma  is  badly  preserved  owing  to  auto-digestion, 
and  the  head  appears  to  show  a  slight  grade  of  chronic 


396       The  Pancreas:  Its  Surgery  and  Pathology 

interstitial  pancreatitis  of  the  interlobular  type.  Through- 
out the  sections  the  islands  of  Langerhans  are  found 
with  difficulty,  and,  from  comparisons  with  other  sections, 
their  number  in  the  tail  sections  at  all  events  appears 
to  be  diminished.  Two  of  the  islands  of  Langerhans 
found  in  the  tail  sections  are  very  large  in  size.  The 
cells,  however,  are  rather  broken  up,  and  into  one  of  them 
haemorrhage  has  occurred.  Minute  changes  are  not  rec- 
ognisable owing  to  bad  preservation  of  the  tissue.  The 
epithelium  of  Wirsung's  duct  shows  distinct  signs  of  a 
catarrhal  change. 

"Summary. — The  condition  is  one  of  acute  pancrea- 
titis, with  haemorrhage  and  necrosis  (the  acute  form  of 
haemorrhagic  pancreatitis  in  Mayo  Robson's  classifica- 
tion)." 

Owing  to  Dr.  Fison's  kindness  we  are  able  to  show 
photographs  of  the  extensive  fat  necrosis  found  in  his 
case  (see  Figs.  87,  88). 

The  following  is  a  case  of  gangrenous  pancreatitis  due 
to  gall-stones,  which  recovered  after  operation: 

Mr.  S ,  aged  fifty-eight,   had  for   six  years  been 

subject  to  paroxysmal  attacks  of  acute  pain,  starting 
in  the  right  hypochondrium  and  radiating  over  the  ab- 
domen and  through  to  the  right  scapula,  the  attacks 
being  accompanied  by  vomiting  and  more  or  less  collapse. 
On  several  occasions  he  had  passed  small  gall-stones. 

About  ten  weeks  before  being  seen  by  one  of  us  he  was 
seized  with  an  attack  which  did  not,  as  usual,  yield  to 
morphia.  The  liver  became  enlarged  and  tender;  there 
was  a  great  amount  of  flatulence  and  acidity  and  a  feeling 
of  discomfort  generally.  After  this  seizure  he  had  ague- 
like attacks  and  jaundice  of  varying  intensity,  and  from 
that  time  a  tumour  steadily  developed  in  the  epigastric 
and  right  hypochondriac  regions.  He  rapidly  lost  flesh 
and  strength,  and  when  he  was  taken  into  a  surgical  home 
for  operation  he  was  so  feeble  and  emaciated  that  it  was 
questionable  whether  he  would  be  strong  enough  to  bear 
it.  Jaundice  was  well  marked,  and  the  tumour  in  the 
upper  abdomen,  which  was  tense,  tender,  and  fluctuating, 
was  still  enlarging.     He  had  had  diarrhoea  six  times  a 


Acute  Pancreatitis  and  Subacute  Pancreatitis    397 

day  for  several  days  before  admission,  and  the  motions 
were  bulky  and  pale  and  contained  fat.     The  urinary 
pancreatic  reaction  was  well  marked.     Just  before  oper- 
ation    he     vomited     clear 
fluid,   not  containing  bile. 
Operation   was    performed 
on  April   5,  1902,  when   a 
pancreatic    cyst    was     ex- 
posed between  the   stom- 
ach and  colon,  containing 
four    pints    of    straw-col- 
oured   fluid.       Inside    the 

cyst  was   found   a   mottled  Fig.   128.— Slough  of  the  pan- 

black    slough    with    grey      StS^Tovll  Col^'StrgeL" 

patches,     2^     to     3     mches        Museum,  2834  B). 

long  by  ij  inches  broad, 

and  ^  inch  thick,  evidently  pancreas.  (See  Figs.  128  and 
129.)  The  gall-bladder  and  ducts  contained  thirty  stones, 
two  the  size  of  walnuts.  One  of  these  was  found  at  the 
junction  of  the  cystic  and  common  duct,  and  pressing  on 

the  latter.     The  cysts 

-,^ .  of    the    pancreas   and 

.St  "^v     ^f.^  •     •  the  gall-bladder  were 

.-**:.',    ^-      '•'• '  dramed    by    separate 

4,1^4      ■       '  f  .  •  tubes,  with  the  stom- 

'     .-  .  J  ,     •■"...  ach  and  the  first  part 

*  '''   ,'    -      .  ■'  '•        of  the  duodenum  be- 

5"**"       '..       -',',,  ^  _,:,       tween   them.     On  be- 

**      ^      %r    ;,''■-  .,         ing  put   back   to  bed 

:     ' .  '  t'.\    :      .^  !'■"        the  patient  was  quiet, 

^  .'        "^"f^  .^  -         but  vomited  frequent- 

^-^^  '  ,  •/*  ly.     He  made  a  steady 

<j^    •  --  -    "  "      :>', .        •  recovery  without  any 

'^X*-    ^       .     ''  '  untoward     symptoms, 

^ ;.       .  .  and     left     for     home 

on  May  2,  1903.      On 

Fig.  129.— Microphotograph  of  ne-         Marrh   i     inn  a    the  r.a 
erased    pancreas    shown    in    Fig.     128         Marcn  3,  1904,  tne  pa 

(X  40).  tient  was  the  picture 

of  health,  and  had 
gained  i^  stones  in  weight.  He  states  that  the  gall- 
bladder opening  had  closed  in  six  weeks  and  the  pancre- 
atic fistula  in  nine  weeks. 


398       The  Pancreas:  Its  Surgery  and  Pathology 

Although  gall-stones  would  appear  to  be  the  most  fre- 
quent cause  of  acute  pancreatitis,  yet  the  following  cases 
operated  on  by  one  of  us  show  that  other  conditions  may 
cause  it. 

In  the  case  of  a  young  woman  suffering  from  acute 
suppurative  pancreatitis  the  viscera  were  found  hope- 
lessly matted  together  and  there  was  extensive  fat  necro- 
sis all  over  the  abdomen.  There  was  no  definite  history 
of  gall-stones,  nor  could  any  be  found  at  the  time  of  the 
operation.  A  subphrenic  abscess  containing  masses  of 
necrosed  fat  and  dark  pus  was  evacuated  and  drained. 
This  only  gave  temporary  relief  to  the  patient,  who  suc- 
cumbed on  the  third  day  after  operation,  apparently 
from  septic  absorption. 

In  another  case,  a  young  man,  aged  twenty-eight, 
slipped  and  fell  forward  against  a  board  projecting  from 
the  end  of  a  table  at  which  he  was  working.  The  blow 
was  comparatively  slight  and  the  man  did  not  fall  to  the 
ground.  Acute  pancreatitis  followed  on  what  was  prob- 
ably a  mere  bruising  of  the  pancreas,  followed  by  slight 
bleeding  into  the  gland,  but  the  effusion  becoming  in- 
fected, acute  hemorrhagic  pancreatitis  supervened.  An 
exploration  for  the  cause  of  the  peritonitis  resulted  in 
the  discovery  of  a  large  collection  of  highly  blood-stained 
fluid  in  the  lesser  peritoneal  sac,  some  of  which  had  burst 
through  a  small  laceration  in  the  omentum  into  the  greater 
sac  of  the  peritoneum.  There  was  general  peritonitis 
present  at  the  time  of  operation,  and  though  drainage 
was  freely  adopted  both  from  the  front  and  through  the 
loin,  the  patient  did  not  survive  many  hours. 

In  the  one  case  extension  of  infection  from  the  duode- 
num was  probably  the  cause ;  in  the  other,  traumatism ; 
but  metastasis  from  mumps,  blood  conditions,  and  in- 
fection from  various  diseases,  such  as  typhoid  fever, 
pyaemia,  etc.,  may  be  the  cause,  as  in  cases  reported  later. 

Diagnosis. — The  diagnosis  of  acute  pancreatitis  is  at 
first  difficult,  as  the  symptoms  are  only  characteristic 
of  peritonitis  starting  in  the  upper  part  of  the  abdomen. 


Acute  Pancreatitis  and  Subacute  Pancreatitis    399 

Fitz's  rule  is  worth  bearing  in  mind:  "Acute  pancreatitis 
is  to  be  suspected  when  a  previously  healthy  person,  or 
sufferer  from  occasional  attacks  of  indigestion,  is  suddenly 
seized  with  violent  pain  in  the  epigastrium,  followed  by 
vomiting  and  collapse,  and,  in  the  course  of  twenty-four 
hours,  by  a  circumscribed  epigastric  swelling,  tympanitic 
or  resistant,  with  slight  rise  of  temperature."  In  case  of 
laparotomy  the  presence  of  extensive  fat  necrosis  is 
almost  pathognomonic. 

At  first  the  dift'erential  diagnosis  must  be  made  from 
intestinal  obstruction,  perforating  duodenal  or  gastric 
ulcer,  ruptured  gall-bladder  or  bile-ducts,  phlegmonous 
cholecystitis,  and  gangrenous  appendicitis.  In  consider- 
ing the  difficulty  of  diagnosing  between  acute  pancrea- 
titis and  intestinal  obstruction  it  has  to  be  borne  in 
mind  that  the  two  may  coexist,  as  the  swollen  pancreas 
may  embrace  and  strangle  the  duodenum,  or  a  collec- 
tion of  inflammatory  material  may  seriously  compress 
it.  The  swelling  will,  however,  be  usually  less  general  in 
pancreatitis  than  in  obstruction,  and,  even  if  the  bowels 
will  not  move,  flatus  can  generally  be  passed.  In  case  of 
doubt,  exploration  may  reveal  fat  necrosis.  In  perfora- 
tion of  a  duodenal  or  gastric  ulcer  there  will  generally 
have  been  premonitory  symptoms  pointing  to  the  disease 
before  the  perforation  actually  occurs,  and  almost  immed- 
iately an  absence  of  liver  dulness  may  be  found.  In 
acute  ptomaine  poisoning  the  history,  the  more  general 
character  of  the  pain,  and  the  presence  of  diarrhoea  will 
usually  help  the  diagnosis. 

In  phlegmonous  cholecystitis  the  symptoms  are  usually 
preceded  by  a  swelling  and  well-marked  tenderness  be- 
neath the  right  costal  margin,  at  first  distinctly  localised 
and  only  later  extending  to  the  epigastrium  and  umbilical 
region,  where  the  tenderness  is  generally  found  in  acute 
pancreatitis  from  the  beginning  of  the  illness ;  moreover, 
the  history  of  gall-stones  will  usually  be  elicited.     In 


400       The  Pancreas:  Its  Surgery  and  Pathology 

appendicitis  the  tenderness  below,  and  to  the  right  of, 
the  umbilicus  and  the  swelling  in  that  region  usually 
remove  the  difficulty  created  by  the  pain  in  both  appendi- 
citis and  pancreatitis,  being  frequently  felt  at  first  just 
above  the  umbilicus.  In  acute  pancreatitis  the  excru- 
ciating pain,  at  first  epigastric  but  later  general,  the  ex- 
tremely rapid  loss  of  weight,  and  the  irregular  tenderness 
opposite  to,  and  above,  the  umbilicus  are  usually  charac- 
teristic. Halsted  lays  stress  on  two  symptoms— the 
excessive  pain  and  cyanosis  of  the  face  and  of  the  abdom- 
inal wall.  The  former  symptom  is  universal,  but  the 
latter  has  not  usually  been  present  in  the  cases  we  have 
seen.  The  urinary  test  for  the  '  'pancreatic  crystals"  should 
not  be  neglected,  as  a  positive  reaction  has  been  obtained 
in  all  the  cases  of  acute  pancreatitis  in  which  we  have 
had  the  opportunity  of  employing  it.  Glycosuria  is 
usually  absent,  but  in  two  out  of  forty-one  cases  of  hsem- 
orrhagic  and  in  three  out  of  forty  cases  of  gangrenous 
pancreatitis  Korte  found  it  present. 

Treatment. — -The  pain  at  the  onset  is  so  acute  as  to 
necessitate  the  administration  of  morphine,  and  the 
collapse  will  probably  demand  stimulants,  which,  on  ac- 
count of  the  associated  vomiting,  may  have  to  be  given 
by  enema.  In  the  early  stages  the  symptoms  may  be 
so  indefinite  that  the  indications  for  surgical  treatment 
are  often  not  clear  enough  to  demand  immediate  opera- 
tion, but  as  soon  as  acute  pancreatitis  is  suspected,  as 
it  may  be  by  the  combination  of  symptoms  together  with 
the  urinary  test,  the  surgeon  must  not  wait  until  the 
collapse  has  passed  off,  as  that  may  be  dependent  on 
septic  absorption  which  can  only  be  relieved  by  operation. 
The  simulation  of  intestinal  obstruction  will  probably 
lead  to  efforts  to  secure  an  evacuation  of  the  bowels  and 
relief  to  the  distension.  Just  as  in  perforative  or  gan- 
grenous appendicitis  an  early  evacuation  of  the  septic 
matter  is  necessary  to  recovery,  so,  in  this  equally  lethal 


Acute  Pancreatitis  and  Subacute  Pancreatitis    401 

affection,  an  early  exploration  from  the  front  through 
the  middle  line  above  the  umbilicus  or  from  behind 
through  the  left  costo-vertebral  angle  is  indicated,  in 
order,  if  possible,  to  relieve  tension,  to  evacuate  septic 
material,  to  secure  free  drainage,  and  to  arrest  the  haem- 
orrhage which  leads  to  disintegration  and  necrosis  of  the 
pancreas.  The  after-treatment  will  be  chiefly  directed 
to  combating  shock  and  keeping  up  the  strength  until 
the  materies  morhi,  both  local  and  general,  can  be  thrown 
off.  Even  if  no  pus  be  found  no  harm  should  accrue 
from  such  an  exploration,  which  can  be  made  in  a  few 
minutes  through  an  incision  in  the  middle  line  above  the 
umbilicus.  After  establishing  the  diagnosis  by  the  dis- 
covery of  a  swelling  in  the  region  of  the  pancreas  with 
effusion  of  blood  and  associated  with  fat  necrosis,  a 
posterior  incision  in  the  left  costo-vertebral  angle  will 
sometimes  enable  the  diseased  organ  to  be  very  freely 
drained  for  the  evacuation  of  pus  and  gangrenous  material 
without  risk  to  the  general  peritoneal  cavit}^  and  with 
little  danger  of  retained  septic  matter,  as  the  drainage 
will  be  a  dependent  one.  If,  however,  the  inflammatory 
collection  of  the  tensely  distended  and  inflamed  gland  be 
incised  from  the  front,  as  is  advisable  in  certain  cases, 
gauze  packing  and  gauze  drainage  may  usually  be  relied 
on  to  prevent  general  infection  of  the  peritoneum.  If 
there  are  signs  of  an  obstructed  common  bile-duct,  the 
gall-bladder  should  be  drained,  and  if  gall-stones  be  dis- 
covered they  should  be  removed,  if  this  can  be  done 
without  seriously  adding  to  the  length  of  the  operation 
or  imperilling  life  by  adding  to  the  shock ;  otherwise  they 
may  be  left  and  removed  on  a  subsequent  occasion  if 
free  drainage  of  the  bile-passages  can  be  secured.  We 
have  had  six  cases  of  acute  pancreatitis  under  our  care 
and  have  operated  on  four,  of  which  two  recovered.  Of 
the  two  cases  where  operation  was  not  consented  to,  and 
where  medical  treatment  alone  was  carried  out,  death 
26 


402       The  Pancreas:  Its  Surgery  and  Pathology 

occurred  in  the  first  case  on  the  third  day  and  in  the 
second  case  after  a  week's  illness,  attended  in  both  with 
great  pain  and  incessant  vomiting. 

In  a  case  of  gangrenous  pancreatitis  in  a  man,  aged 
fifty-eight,  a  collection  of  fiuid  was  opened  through  the 
great  omentum,  above  the  hepatic  flexure  of  the  colon, 
and  a  slough  of  the  pancreas  was  extracted,  after  which 
free  drainage  was  established.  At  the  same  time  the  gall- 
bladder and  all  the  stones  within  reach  were  removed, 
but  the  common  duct  was  not  opened,  as  the  patient  was 
too  ill  to  bear  a  prolongation  of  the  operation.  Fortu- 
nately, several  small  calculi  worked  back  through  the 
tube  in  the  gall-bladder  and  recovery  was  not  delayed 
and  was  ultimately  complete.  The  pancreatic  reaction 
was  well  marked  in  this  case. 

In  another  case  of  a  young  married  woman  suffering 
from  acute  suppurative  pancreatitis  the  viscera  were 
found  hopelessly  matted  together.  There  was  extensive 
fat  necrosis  all  over  the  abdomen.  A  subphrenic  abscess 
containing  masses  of  necrosed  fat  and  dark  pus  was  evacu- 
ated. The  patient  was  only  temporarily  relieved  and 
succumbed  on  the  third  day.  In  this  case  it  would  prob- 
ably have  been  better  to  have  drained  through  the  costo- 
spinal  angle  on  the  left  side  as  well  as  from  the  front, 
but  the  patient  was  so  ill  that  it  did  not  appear  to  be  ad- 
visable to  do  more  lest  death  should  occur  on  the  table. 

In  a  case  of  traumatic  haemorrhagic  pancreatitis  in  a 
man,  aged  twenty-eight,  drainage  through  the  loin  as  well 
as  in  front  was  adopted,  but  did  not  save  life,  as  at  the 
time  of  operation  peritonitis  was  already  advanced,  and 
involved  both  the  greater  and  lesser  peritoneal  sacs. 

In  another  case,  of  a  middle-aged  medical  man,  who 
was  seen  with  Dr.  H.  P.  Hawkins,  the  diffuse  fat  necrosis 
and  adhesions  of  the  viscera  and  omentum  into  a  dense 
mass  presented  a  formidable  obstacle  to  complete  ex- 
ploration, but  as  no  evidence  of  any  collection  of  fiuid 
either  in  the  pancreas  or  in  the  lesser  peritoneal  sac  could 
be  obtained,  and  as  no  gall-stones  could  be  felt  in  the 
gall-bladder  or  bile-ducts,  the  peritoneal  toilet  was  per- 
formed and  the  abdomen  closed,  recovery  following  and 
ending  in  complete  restoration  to  health.     It  is  worthy 


Acute  Pancreatitis  and  Subacute  Pancreatitis    403 

of  note  that  in  this  case  the  diagnosis  was  confirmed  before 
operation  by  the  urinary  pancreatic  reaction. 

A  case  was  reported  by  Dr.  Charles  D.  Muspratt,  of  a 
woman,  aged  forty  years,  who  had  been  admitted  to  the 
Royal  Victoria  Hospital,  Bournemouth,  on  December  3. 
1903,  in  a  state  of  collapse  and  suffering  from  severe  ab- 
dominal pain  with  incessant  vomiting.  The  abdomen 
was  opened  within  twenty-four  hours  of  the  onset  of 
acute  symptoms  and  the  omentum  and  intestines  in  the 
neighbourhood  of  the  pancreas  were  found  deeply  blood- 
stained with  numerous  spots  of  fat  necrosis.  The  pan- 
creas was  almost  purple  and  extremely  tense.  An  incision 
was  made  into  the  dark  gland  and  very  free  bleeding  fol- 
lowed which  was  arrested  by  ligature.  Gauze  drainage 
was  employed  and  complete  recovery  followed. 

This  is  apparently  the  first  case  in  which  direct  incision 
of  the  pancreas  was  adopted,  and  the  operator  is  to  be 
congratulated  not  only  on  having  had  the  strength  of  his 
convictions  in  treating  acute  hemorrhagic  pancreatitis 
on  the  lines  of  other  phlegmonous  inflammations,  but  on 
the  success  of  such  treatment.  In  a  case  reported  by 
von  Mikulicz  in  1903,  a  patient,  under  the  care  of  Dr. 
C.  B.  Porter,  of  Boston,  was  operated  on  by  a  deep  in- 
cision into  the  inflamed  gland,  with  an  excellent  result. 
This  is  apparently  the  second  case  in  which  the  pancreas 
was  deliberately  incised  during  acute  inflammation  with 
a  successful  result.  Woolsey  gives  a  summary  of  three 
cases  of  this  affection  successfully  dealt  with  by  laparot- 
omy and  drainage.  The  first  two  cases  were  operated 
on  in  the  early  stage — the  first  on  the  third  day  and  the 
second  twelve  hours  after  the  onset.  The  first  case  was 
a  hsemorrhagic  one  and  showed  fat  necrosis;  the  second 
case  showed  no  fat  necrosis  or  bloody  fluid,  but  the  latter 
appeared  on  the  removal  of  the  gauze  drain  two  days  after 
the  operation.  In  the  third  case  there  was  marked  but 
temporary  glycosuria.  Dr.  C.  G.  B.  Kempe,  of  Salisbury, 
on  December  11,  1902,  excised  a  portion  of  the  head  of 


404       The  Pancreas:  Its  Surgery  and  Pathology 

the  pancreas  affected  with  acute  haemorrhagic  pancrea- 
titis. It  was  done  within  two  hours  of  the  onset  of  haem- 
orrhage. The  patient  unfortunately  died  from  diarrhoea 
fifteen  days  later.  The  argument  that  the  percentage 
of  mortality  will  be  less  if  the  surgeon  waits  for  the  for- 
mation of  a  local  abscess  is  fallacious,  as  it  takes  no  con- 
sideration of  the  large  percentage  of  those  who  die  before 
such  a  favourable  result  is  presented;  and,  in  the  second 
place,  many  patients  never  develop  a  local  abscess,  the 
process  being  diffuse  from  the  onset.  The  high  mortality 
of  early  operation  in  acute  cases  is  due  to  the  fact  that 
in  many  of  these  fatal  instances  intestinal  obstruction 
was  suspected  and  the  collapsed  patients  were  subjected 
to  a  prolonged  search  for  the  seat  of  the  supposed  lesion. 
Of  fifty-nine  reported  cases  of  operation  during  the  acute 
stage,  twenty-three  recovered ;  these  include  the  cases  just 
described.  Although  this  is  a  large  mortality,  it  must  be 
borne  in  mind  that  the  disease  is  a  lethal  one  and  usually 
ends  in  death  if  not  treated  surgically.  The  lessons  which 
one  may  learn  from  recorded  cases  are  not  to  wait  until 
the  system  is  over-weighted  with  absorbed  poison  before 
operating  and  not  to  spend  too  long  a  time  over  the 
operation. 

SUBACUTE  PANCREATITIS 

Although  no  hard-and-fast  line  can  be  drawn  between 
acute  and  subacute  pancreatitis,  yet  the  less  acute  onset, 
the  longer  course,  the  limitation  of  the  suppurative  proc- 
ess by  lymph  barriers,  and  the  much  more  hopeful  out- 
look as  the  result  of  treatment  present  so  many  differences 
that  clinical  observers  will  acknowledge  that  such  a  divi- 
sion is  desirable,  from  the  point  of  view  of  both  diag- 
nosis and  treatment.  Acute  pancreatitis  seems  to  bear  the 
same  relation  to  subacute  pancreatitis  that  a  diffuse  mas- 
titis does  to  a  simple  abscess  of  the  breast,  or  a  diffuse 
suppurative  parotitis  to  a  simple  parotid  abscess. 


Acute  Pancreatitis  and  Subacute  Pancreatitis    405 

It  may  have  a  more  or  less  sudden  onset,  with  acute  pain 
and  vomiting,  and  may  be  associated  with  constipation, 
but  collapse  is  not  a  marked  symptom  and  is,  as  a  rule, 
absent.  The  upper  abdominal  region  does  not  become 
so  rapidly  distended  and  vomiting  is  less  severe  and  less 
prolonged.  At  other  times,  and  this  is  generally  the  case, 
the  onset  is  more  gradual,  though  the  symptoms  may  be 
similar.  As  gall-stones  are  the  usual  cause  of  this  form 
of  pancreatitis,  a  history  of  intermittent  attacks  of  spasms, 
at  first  without  and  later  accompanied  by  jaundice,  will 
be  elicited,  and  before  the  onset  of  pancreatic  trouble  the 
symptoms  of  infective  cholangitis,  in  the  shape  of  rigors 
with  deepening  of  jaundice  and  with  intermittent  fever, 
will  generally  be  found.  Tenderness  over  the  pancreas 
is  well  marked,  and  on  account  of  the  tympanites  being 
less  than  in  the  acute  form,  it  may  be  possible  to  feel  the 
swollen  gland,  especially  under  an  ansesthetic,  and  as  the 
case  progresses  a  definite  tumour  often  develops.  Con- 
stipation gives  place  to  diarrhoea,  and  pus  or  blood  may 
be  noticed  in  the  stools,  which  have  a  very  foetid  odour 
and  usually  contain  fat  and  undigested  muscle  fibres. 
The  pulse  is  not  so  seriously  affected  as  in  the  acute  form 
and  the  temperature  is  more  irregular.  The  temperature 
may  reach  104°  or  105°  F.  and  yet  the  pulse  may  only 
vary  between  70  and  no.  The  morning  temperature 
may  be  normal  and  the  evening  temperature  high  for 
several  days  or  even  weeks.  Rigors  or  chills  usually 
occur  and  may  be  repeated  from  time  to  time.  The  pain 
occurs  in  paroxysms,  but  there  is  also  a  constant  dull 
pain  at  the  epigastrium.  The  patient  may  lose  the  more 
urgent  symptoms  and  appear  to  be  really  improving,  but 
the  loss  of  flesh  and  feebleness  continue,  and  relapses 
usually  occur,  leaving  the  patient  each  time  more  and 
more  feeble  until  death  supervenes  from  asthenia.  Albu- 
minuria is  pretty  constant,  but  glycosuria  is  rarely  present. 
The  pancreatic  reaction  in  the  urine  is,  as  a  rule,  well 


4o6       The  Pancreas:  Its  Surgery  and  Pathology 

marked.  If  an  abscess  develop,  the  pus  may  form  a 
tumour  projecting  in  the  superior  abdominal  region  and 
forming  a  tender  swelling  behind  the  stomach,  or  per- 
haps coming  to  the  surface  above  or  below  that  viscus; 
or  it  may  burrow  into  either  loin,  forming  a  perirenal 
abscess,  or  passing  under  the  diaphragm  it  may  form  a 
subphrenic  abscess.  Occasionally  the  pus  may  follow 
the  psoas  muscle  and  form  a  subperitoneal  abscess  in 
the  iliac  region,  or  even  passing  over  the  brim  of  the  pel- 
vis it  may  collect  in  the  left  broad  ligament. 

Sometimes  the  abscess  bursts  into  the  stomach  and  is 
vomited,  or  into  the  bowel  and  is  voided  per  anum,  after 


Fig.  130. — Abscess  of  the  pancreas. 

which  diarrhoea  may  continue  and  pus  may  be  seen  from 
time  to  time  as  any  fresh  collection  forms  and  bursts. 
With  the  evacuation  of  the  abscess,  relief  occurs  for  a 
time  and^  the  temperature  improves,  but  relapses  usually 
take  place  and  a  mild  form  of  septicaemia  persists  with 
a  hectic  temperature.  Death  is  the  usual  termination 
unless  an  operation  be  done,  though  spontaneous  recovery 
may  possibly  occur  after  a  tedious  and  prolonged  illness 
should  the  abscess  burst  into  the  bowel  or  be  otherwise 
safely  evacuated. 

For  the  diagnosis  of  subacute  pancreatitis  in  its  initial 


Acute  Pancreatitis  and  Subacute  Pancreatitis    407 

stages  little  need  be  added  to  what  has  already  been  said 
when  considering  suppurative  catarrh  and  acute  phleg- 
monous pancreatitis.  The  presence  of  a  tumour  or  of 
a  diffuse  epigastric  swelling  behind  the  stomach  will  be 
generally  found,  or  if  epigastric  tenderness  prevents  pal- 
pation, an  anassthetic  will  enable  the  swelling  to  be  felt. 
There  is  usually  fever  of  a  septic  type.  The  presence  of 
leucocytosis  and  the  discovery  of  the  pancreatic  reaction 
in  the  urine  will  afford  valuable  aids  to  diagnosis.  As 
soon  as  an  abscess  forms  it  may  reach  the  surface  above 
or  below  the  stomach,  in  either  loin,  in  the  left  iliac  region, 
under  the  diaphragm,  or  even  in  the  pelvis,  and  will 
require  differential  diagnosis  from  other  conditions  lead- 
ing to  a  collection  of  pus  in  those  situations,  such  as  chronic 
perforative  gastric  or  duodenal  ulcer,  suppurative  chole- 
cystitis, splenic  abscess,  perirenal  abscess,  spinal  abscess, 
glandular  abscess,  etc. 

Treatment. — The  subacute  form  of  pancreatitis  is  more 
amenable  to  treatment,  as  the  indications  are  so  much 
more  definite  and  there  is  more  time  for  careful  considera- 
tion. Though  it  has  usually  been  attacked  only  when  an 
abscess  has  formed  and  is  manifestly  making  its  way  to 
the  surface,  yet  there  is  no  reason  why  in  some  cases 
surgical  treatment  should  not  be  adopted  at  an  earlier 
stage.  As  in  the  acute  condition,  morphine  may  be  re- 
quired to  relieve  the  pain  and  to  lessen  the  collapse. 
Distension,  if  present,  demands  attention,  and  may  have 
to  be  relieved  by  lavage  of  the  stomach  and  turpentine 
enemata  or  by  the  administration  of  calomel  by  the  mouth. 
Calomel  is  also  of  benefit  as  an  intestinal  antiseptic,  for 
which  purpose  it  may  be  given  in  small  repeated  doses 
followed  by  a  saline  aperient.  As  soon  as  the  constipa- 
tion is  relieved,  diarrhoea  is  apt  to  supervene,  when  salol 
and  bismuth,  with  small  doses  of  opium,  may  be  given. 
If  surgical  treatment  is  decided  on,  a  median  incision 
above  the  umbilicus  will  enable  the  operator  to  palpate 


4o8       The  Pancreas:  Its  Surgery  and  Pathology 

the  pancreas  and  to  locate  any  incipient  collection  of 
pus,  which,  if  practicable,  should  then  be  evacuated  by  a 
posterior  incision  in  the  left  or  right  costo-vertebral 
angle.  If  the  posterior  incision  be  thought  impracticable, 
the  collection  of  pus  may  be  removed  by  aspiration  and 
the  cavity  opened  and  packed  with  gauze,  which  may  be 
brought  forwards  through  a  large  rubber  tube,  which 
procedure  will,  in  the  course  of  from  twenty-four  to  forty- 
eight  hours,  establish  a  track  isolated  from  the  general 
peritoneal  cavity. 

In  abscess  of  the  pancreas,  which  usually  assumes 
the  form  of  subacute  pancreatitis,  and  which  we  must 
distinguish  from  the  acute  suppurative  pancreatitis  where 
the  pus  is  diffused  through  the  gland  or  where  the  ab- 
scesses are  small  and  multiple,  the  suppurating  process 
is  limited  by  a  pouring  out  of  lymph,  so  that  should 
the  patient  survive  the  initial  more  acute  stage  and 
discovery  of  the  pus-containing  cavity  be  made,  the 
condition  is  one  decidedly  amenable  to  treatment  by 
drainage.  The  anatomical  relation  will  readily  explain 
the  course  along  which  the  pus  burrows  should  it  burst 
through  its  lymph  barriers — for  instance,  in  one  case  an 
abscess  formed  and  was  opened  in  the  right  loin  of  a  young, 
man,  aged  twenty-four  years,  that  had  been  mistaken 
for  a  perirenal  abscess,  yet  the  kidney  was  quite  healthy 
and  the  grumous  pus  had  come  from  the  pancreas  and 
passed  behind  the  peritoneum  covering  the  second  part 
of  the  duodenum.  The  patient  recovered  completely. 
In  another  case  an  abscess  was  opened  in  the  left  iliac 
region  that  had  apparently  started  from  the  body  of  the 
pancreas  and  which  had  burrowed  in  the  same  way  be- 
hind the  peritoneum.  The  patient  recovered  from  the 
operation,  but  developed  trouble  in  the  left  side  of  the 
thorax  and  died  suddenly  several  weeks  later.  In  one 
case  the  abscess  was  subphrenic.  In  another,  where  the 
symptoms  were  rather  acute  and  the  patient  was  ex- 


Acute  Pancreatitis  and  Subacute  Pancreatitis    409 

tremely  ill,  pus  was  discovered  between  the  liver  and  the 
stomach,  and  although  drainage  was  apparently  complete, 
the  patient  succumbed  in  a  few  days  to  exhaustion  due 
to  the  septic  process  that  had  been  initiated  before  the 
abscess  was  opened.  In  two  other  cases,  the  sequence  of 
suppurative  catarrh,  abscesses  of  the  pancreas  were 
successfully  drained  through  a  tube  in  the  common  bile- 
duct  after  removing  the  gall-stones  which  had  obstructed 
Wirsung's  duct.  In  one  of  these  cases  the  patient,  a 
woman,  aged  seventy-two  years,  remained  quite  well, 
but  in  the  other  a  man,  aged  forty  years,  recovered  from 
the  operation,  but  three  months  afterw^ards  died  from 
exhaustion,  and  at  the  necropsy  the  empty  abscess  cavity 
was  discovered  in  the  head  of  the  pancreas,  the  rest  of 
the  gland  being  affected  with  chronic  interstitial  inflam- 
mation. In  one  case — a  man,  aged  thirty-five  years^a 
pancreatic  abscess  burst  into  the  stomach,  setting  up 
acute  gastritis,  the  condition  having  been  proved  b}^  an 
exploratory  operation.  It  was  treated  by  gastro-enteros- 
tomy  to  drain  away  the  foul  stomach  contents.  The 
patient  is  now  quite  well,  eight  years  later.  In  another 
case,  in  a  young  married  woman,  aged  twenty-six  years, 
the  abscess  apparently  burst  into  the  bowel,  and,  though 
recovery  was  tardy,  she  ultimately  got  quite  well  without 
operation.  The  diagnosis  was  made  from  the  symptoms 
and  by  an  examination  of  the  swollen  pancreas  under  an 
anaesthetic  and  subsequently  by  the  presence  of  a  pan- 
creatic reaction  in  the  urine.  It  is  important  in  these 
cases  to  see  that  the  cause  is  removed,  if  that  be  possible — ■ 
for  instance,  gall-stones  or  pancreatic  calculi — so  that  if 
recovery  occurs  there  may  be  no  fear  of  relapse. 

It  will  thus  be  seen  that  out  of  eight  cases  of  abscess 
of  the  pancreas,  one  of  which  was  mentioned  under  acute 
pancreatitis,  six  were  operated  on,  with  recovery  from 
operation  in  five,  though  in  one  of  the  cases  the  relief  was 
only  for  a  few  weeks  and  in  another  for  a  few  months. 


4IO       The  Pancreas:  Its  Surgery  and  Pathology 

In  the  eighth  case,  which  was  not  operated  on,  the  abscess 
burst  into  the  bowel  and  was  discharged,  the  diagnosis 
having  been  made  by  an  examination  of  the  tumour  under 
an  aneesthetic  and  by  the  presence  of  the  pancreatic 
reaction. 

When  inflammation  of  the  pancreas  has  ended  in  ab- 
scess, chronic  interstitial  pancreatitis  will  also  probably 
be  present,  as  was  shown  at  the  necropsy  of  one  case  that 
died  some  months  subsequently.  It  is  possible  that  in 
some  cases  the  interstitial  change  may  be  local,  though  in 
others  it  will  be  general  and  may  then  lead  to  atrophy  of 
the  gland  and  to  glycosuria. 

A  search  through  literature  reveals  a  considerable 
number  of  pyasmic  abscesses  of  the  pancreas,  but  those 
resulting  from  subacute  pancreatitis  have  been  rarely 
recorded.  Besides  seven  operations  for  abscess  of  the 
pancreas  with  two  deaths  above  referred  to,  there  have 
been  seven  others  recorded  with  three  deaths.  Thus, 
of  fourteen  cases  five  died,  giving  a  mortality  of  35.6  per 
cent. 

Literature 

Babler:   St.  Louis  Courier  of  Med.,  Nov.,  1905. 

Baines:   Brit.  Med.  Journ.,  Feb.  lo,  1906. 

Barling:   Brit.  Med.  Journ.,  Dec.  22,  1900;    Ibid.,  Feb.  24,  1906. 

Brennecke:   Journ.  Amer.  Med.  Assoc.,  June  4,  1898. 

Brown,  W.  H.:   Lancet,  Sept.  26,  1903;   Ibid.,  Aug.  13,  1904. 

Bryant:   Lancet,  Nov.  10,  1900. 

Bunting:   Johns  Hopkins  Hosp.  Bull.,  Aug.,  1906. 

Classen:    "  Krankheit.  der  Bauchspeicheldruse,"  Koln,  1843. 

Cooke:   Brit.  Med.  Journ.,  May  19,  1906. 

Deanesly:   Lancet,  July  i,  1899. 

Deaver:  Med.  News,  March  5,  1904. 

Deaver  and  Muller:   American  Medicine,  March  19,  1904. 

Drasche:   Ber.  der  k.  k.  Krank.,  Wien,  1886. 

Durno:  Lancet,  Nov.  10,  1906. 

Earl:   Brit.  Med.  Journ.,  Nov.  17,  1906. 

Fison:  Lancet,  June  4,  1904. 

Fitz:  Medical  Congress,  Washington,  1903. 

Fletcher:   Prov.  Med.  and  Surg.  Journ.,  1848. 

Friederich:     Ziemssen's  "Handbuch  d.  spec.   Path.  u.  Therap.,"  viii, 

2,  1878. 
Fripp  and  Bryant:   Lancet,  Dec.  17,  1898. 
Frison:    "Recueil.  de  Med.  militaire,"  1876. 
Fuchs:   Deutsch.  med.  Wochen.,  1902,  xxviii,  829. 


Acute  Pancreatitis  and  Subacute  Pancreatitis    411 

Greisclius:   Misc.  Acad,  curios,  1672,  1673,  P-  74- 

Hahn:   Deutsche  med.  Wochen.,  1901,  v,  5. 

Halley:   Scottish  Med.  and  Surg.  Journ.,  Jan.,  1904. 

Halsted:   Johns  Hopkins  Hosp.  Bull.,  1901,  Nos.  121,  122,  123. 

Harvey:    Brit.  Med.  Journ.,  Nov.  17,  1906. 

Heaton:   Brit.  Med.  Journ.,  Dec.  17,  1904. 

Hogarth  and  Moynihan:   Practitioner,  1903,  i,  504. 

Jeffrey:    Lancet,  Jan.  20,  1906. 

Jones,  Littler:   Lancet,  Feb.  18,  1905. 

Kempe:    Brit.  Med.  Journ.,  Feb.  27,  1904. 

Kennan:   Brit.  Med.  Journ.,  Nov.  14,  1896. 

Keyser:    Lancet,  Oct.  19,  1901. 

Kilgow:    Lond.  Journ.  of  Med.,  i860,  p.  1052. 

Klob:   Oester  Zeitsch  f.  prakt.  Heilk.,  i860. 

Korte:   Deutsche,  med.  Woch.,  1901,  v,  6. 

Leusden:   Charitd  Ana.,  xxxi,  1902. 

Lilienthal:   Annals  of  Surgery,  Jan.,  1906. 

Lund:   Boston  City  Hosp.  Rep.,  Dec,  1900. 

Mayo:   Journ.  of  Amer.  Med.  Assoc,  1902,  i,  107. 

Moore:  Trans  Lond.  Path.  Soc,  1882,  xxxiii,  186. 

Morian:   Miinch.  med.  Woch.,  March  14,  1899. 

Munster:   Lancet,  Dec.  30.  1905. 

Muspratt:   Brit.  Med.  Journ.,  Feb.  3,  1901;  Ibid.,  Feb.  6,  1904. 

Norris:   Lancet,  Dec.  9,  1905. 

Nothnagel:     "Encyclo.  of   Prac   Med.,"    "  Dis.   of  Liver,    Pancreat.," 

etc.,  Eng.  tr.,  1903. 
Opie:   "Diseases  of  the  Pancreas,"  1903. 
Osier:   "Practical  Medicine." 

Pauchet:   Rev.  de  Gynec.  et  de.  Chir.  Abdom.,  Nov.,  1905. 
Peiser:    Deut.  Zeit.  f.  Chir.,  1902,  Ixv,  302. 
Percival:   Trans.  Ass.  K.  and  Q.  Phy.  Ireland,  18 18. 
Perle:   Diss.  Berlin,  1807. 

Pitt  and  Jacobson:   Med.  Press  and  Circ,  Dec.  14,  1898,  p.  619. 
Portal:   Cours  d'Anat.  Medicale,  v,  352. 
Reynolds:   Med.  Chron.,  Aug.,  1900,  p.  328. 
Riboli:   Gaz.  de  Sard.,  1858." 

Robson,  Mayo:   Hunterian  Lectures,  Lancet,  Mar.  19,  26,  April  2,  1904. 
Roddick:  Canadian  Med.  Journ.,  1869.  p.  385. 
Selberg:    Berlin  klin.,  1901,  xxxviii,  923. 
Shea:   Lancet,  1881,  p.  791. 

Smith:    Dublin  Journ.  of  Med.  Sci.,  i86"o,  p.  201. 
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Webber:   Lancet,  Aug.  5,  1905. 

Woolsey:      Med.  News,  Dec.  20,  1902;  Annals  of  Surgery,  Nov., 1903. 
Young:    Lancet,  Feb.  10,  1906. 


CHAPTER  XVI 
CHRONIC  PANCREATITIS 

In  a  lecture  delivered  at  the  London  Medical  Grad- 
uates' College  and  Polyclinic  in  July,  1900,  attention  was 
drawn  by  one  of  us  to  chronic  pancreatitis  as  a  clinical 
entity.  An  opinion  was  then  expressed  that  although  it 
had  hitherto  been  scarcely,  if  at  all,  recognised,  except 
as  a  pathological  curiosity,  it  was  not  an  uncommon 
disease.  Since  that  statement  was  made  further  ex- 
perience has  still  more  conclusively  demonstrated  the 
frequency  with  which  the  disease  occurs,  and  how  rarely 
its  presence  is  recognised  in  clinical  practice.  Chronic 
inflammations  of  the  kidneys,  liver,  and  other  organs  give 
rise  to  symptoms  which  are  described  in  every  text-book ; 
but  the  no  less  important  and  characteristic  signs  of 
chronic  pancreatitis  are,  even  in  the  most  recent  medical 
and  surgical  works,  entirely  omitted,  or  awarded  but 
scanty  and  inadequate  notice.  It  is  true  that  the  relation 
of  the  pancreas  to  diabetes  is  now  generally  recognised, 
but  to  wait  until  glycosuria  supervenes  before  making  a 
diagnosis  is  to  throw  away  the  patient's  only  opportunity 
of  cure — an  opportunity  which,  if  taken  sufficiently 
early,  will  in  nearly  all  cases  restore  him  to  perfect  health, 
and  save  him  from  a  lingering  and  painful  illness. 

There  appears  to  be  a  general  belief  in  the  profession 
that  the  symptoms  of  chronic  pancreatitis  are  so  over- 
shadowed by  those  of  other  morbid  states  from  which  it 
may  arise,  or  with  which  it  may  be  associated,  that  it 
can  rarely  be  recognised  during  life  as  a  clinical  entity, 
and  that  even  then  it  is  usually  only  revealed  at  operation 
•undertaken  for  the  removal  of  gall-stones  or  for  other 

412 


Chronic  Pancreatitis  413 

obstructive  condition  in  the  bile-passages.  Opie,  in  his 
work  on  diseases  of  the  pancreas  (p.  163),  states  that  "  the 
lesion  is  seldom  associated  with  such  definite  symptoms 
as  to  be  recognised  during  life,  and  that  even  at  autopsy 
the  condition  is  frequently  overlooked."  The  former 
part  of  this  statement  does  not  hold  good  at  the  present 
day;  for  from  the  inform£ition  obtained  by  a  careful  ex- 
amination of  the  patient,  a  knowledge  of  the  history  of 
the  case,  and  the  results  of  a  chemical  and  microscopical 
examination  of  the  excreta,  a  correct  opinion  may  be 
formed  in  a  large  majority  of  instances.  The  latter  part 
of  Opie's  statement,  however,  is  as  true  today  as  when 
it  was  written.  As  evidence  of  the  difficulty  that  even 
skilled  pathologists  have  experienced  in  recognising  pan- 
creatic disease  by  naked-eye  examination  alone,  one  need 
only  compare  the  statistics  compiled  by  Hale  White 
from  the  Guy's  Hospital  post-mortem  records  for  the 
fourteen  years  1884- 189 7,  and  the  results  of  the  micro- 
scopical examination  of  the  pancreas  in  a  series  of  con- 
secutive cases  by  Bosanquet  (page  127).  From  these 
it  is  evident  that  at  present  it  is  impossible  to  rely  on 
post-mortem  records,  either  ancient  or  even  recent,  for 
precise  information  as  to  the  frequency  with  which  chronic 
inflammation  occurs,  and  that  "unless  a  microscopical 
examination  of  the  pancreas  is  made,  it  is  frequently  im- 
possible to  say  in  any  case  whether  it  is  normal  or  not, 
since  in  many  instances  the  external  appearance  of  the 
gland  may  be  almost  unchanged  in  the  presence  of  con- 
siderable alteration  in  its  anatomy"  (Bosanquet). 

The  surgeon  has  considerable  advantage  over  the  path- 
ologist in  this  respect,  for  he  has  the  opportunity  of  exam- 
ining and  handling  the  living  pancreas,  and,  after  some 
experience,  he  can  generally  tell  the  difference  between 
the  feel  of  the  normal  and  diseased  gland.  A  chronically 
inflamed  pancreas  is  generally  swollen  and  harder  than 
usual.     A  typical  case  conveys  to  the  examining  hand 


414       The  Pancreas:  Its  Surgery  and  Pathology 

the  impression  of  a  hard  waxen  cast.  This  may  be 
recognised  as  a  general  swelling  of  the  whole  gland,  or  as 
a  limited  swelling  involving  the  head  and  body  of  the 
gland.  The  swelling  and  hardness,  especially  in  the  early 
stages  of  catarrhal  inflammation,  are,  no  doubt,  due  to 
engorgement  with  blood  and  retained  secretion ;  but  as  in 
many  cases  this  will  largely  disappear  after  death,  the 
difference  noticed  in  biopsies  and  autopsies  is  easily 
explained.  The  lobules  of  the  gland  have  the  feeling  of 
being  mapped  out  and  differentiated  in  a  manner  very 
different  from  their  state  in  the  ordinary  healthy  organ. 
The  irregularity  and  change  of  consistency  is  occasion- 
ally so  marked  that,  to  the  inexperienced,  it  may  suggest 
malignant  disease.  In  fact,  in  some  of  the  earlier  cases 
of  chronic  pancreatitis  that  came  under  our  notice  this 
was  the  idea  that  suggested  itself  on  examining  the  pan- 
creas during  operation,  and  it  was  only  the  subsequent 
uneventful  recovery  of  a  number  of  these  patients,  fol- 
lowed by  an  immunity  from  any  further  symptoms  of 
disease — an  immunity  which  in  some  instances  has  now 
extended  to  a  considerable  number  of  years — that  con- 
firmed the  suspicion  that  the  condition  was  purely  inflam- 
matory. The  first  case  occurred  in  1890,  and  the  patient, 
a  woman  ast.  forty-four,  is  now  well,  seventeen  years  later. 
Since  the  third  case,  in  1892,  which  was  confirmed  by 
autopsy  and  by  a  microscopical  examination,  the  oppor- 
tunity has  been  taken  of  examining  the  pancreas  in  a  very 
large  number  of  cases  during  operations  in  the  upper  ab- 
domen, and  in  many  of  these  there  was  little  doubt  that 
disease  of  this  organ  contributed  to,  or  was  the  cause  of, 
the  symptoms  complained  of.  The  marked,  and  in  many 
cases  striking,  relief  that  followed  appropriate  operative 
interference  conclusively  demonstrated  the  importance 
of  the  condition ;  and  we  can  point  to  a  large  number  of 
patients,  now  in  perfect  health,  who  before  operation  were 
extremely  ill,  and  in  many  cases  supposed  to  be  suffering 


Chronic  Pancreatitis 


415 


from  malignant  disease  of  the  pancreas,  chronic  catarrh 
of  the  bile-ducts,  cirrhosis  of  the  liver,  cancer  of  the  com- 
mon bile-duct  or  of  the  papilla,  cancer  of  the  liver,  com- 
mon-duct cholelithiasis,  malaria,  and  other  diseases. 

The  number  of  cases  of  chronic  pancreatitis  reported 
in  the  journals  since  attention  was  called  to  the  subject 
in  1900  shows  that  others  are  now  recognising  the  condi- 
tion, and  that,  where  suitable  treatment  has  been  adopted, 


Fig.  131. — Chronic  interstitial  pancreatitis  of  the  interlobular  variety 

(Santos). 


satisfactory  results  have  followed.  Chronic  pancreatitis 
has  also  been  reported  as  occurring  spontaneously  in  the 
lower  animals.  Megnin  and  Nocard  have  described  the 
disease  in  a  horse,  which,  during  life,  suffered  from  weak- 
ness, loss  of  appetite,  constipation,  emaciation,  and 
slight  icterus.  Post-mortem  the  pancreas  was  found  to 
be  indurated,  the  duct  was  dilated  and  filled  with  albu- 
minous material,  and  the  common  bile-duct  was  com- 
pressed, there  was  also  catarrh  of  the  salivary  duct. 


41 6       The  Pancreas:  Its  Surgery  and  Pathology 


The  results  of  chronic  inflammation  of  the  pancreas, 
as  seen  on  the  post-mortem  table  and  following  experi- 
ments on  animals,  may  be  divided  histologically  into: 
(i)  Chronic  interstitial  interlobular  pancreatitis;  (2) 
chronic  interstitial  inter  acinar  pancreatitis;  (3)  cirrhosis 
of  the  pancreas. 

In  the  interlobular  form  of  chronic  interstitial  pan- 
creatitis the  normal  loose  connective  tissue  between  the 

lobules  of  the  gland  is 
converted  into  dense 
sclerotic  material,  the 
glandular  tissue  is  com- 
pressed, and  replaced 
frorn  the  periphery  of 
the  lobule,  by  newly 
formed  connective  tis- 
sue, the  normally  ob- 
scure lobules  becoming 
distinctly  defined. 

In  the  interacinar  va- 
riety a  diffuse  network 
of  irregular  fibrous  tis- 
sue is  found  separating 
the  glandular  acini,  and 
in  some  instances  pene- 
trating between  the  in- 
dividual cells,  while  the 
interlobular     tissue     is 
comparatively  little  affected.     The  gland  is  tough  rather 
than  hard,  and  the  nodular  character  seen  in  the  inter- 
lobular form  is  lacking. 

Cirrhosis  of  the  pancreas  is  the  final  stage  of  either  inter- 
lobular or  interacinar  pancreatitis,  but  it  more  commonly 
occurs  as  a  result  of  chronic  interlobular  inflammation, 
of  which  glycosuria  is  a  rare  sequel,  not  occurring  till  the 
lesion  has  so  far  advanced  that  the  glandular  acini  are 


Fig.  132. — Fibrosis  of  the  pan- 
creas (St.  Thomas'  Hospital  Museum, 
1413  a). 


Chronic  Pancreatitis 


417 


almost  completely  destroyed,  and  the  vascular  supply  of 
the  islands  of  Langerhans  is  seriously  interfered  with  by 
the  pressure  of  the  newly  formed  fibrous  tissue.  In  the 
interacinar  form,  on  the  other  hand,  the  cell  islands  are 
involved  at  a  very  early  stage,  diabetes  quickly  super- 
venes, and  it  may  prove  fatal  before  the  cirrhosis  has  be- 
come very  marked.  A  marked  new-formation  of  fibrous 
tissue  in  the  pancreas  appears  to  be  a  comparatively  late 
result  of  chronic  inflammation,  and  unless  this  fact  is 
borne  in  mind  a  very  incomplete  conception  of  the  condi- 
tion is  liable  to  be 
formed. 

Experimental  liga- 
ture of  the  ducts  in 
animals  has  shown 
that  inflammatory 
atrophy  and  degener- 
ation of  the  secreting 
parenchyma  precede 
and  accompany  the 
formation  of  the  new 
fibrous  tissue  which 
takes  place,  and  in 
chronic  pancreatitis 
due  to  obstruction  of 
the    common   duct   in 

man  the  sequence  of  events  is  no  doubt  the  same.  In 
the  early  stages  the  organ  will  be  engorged  with  blood 
and  retained  secretion,  the  parenchyma  will  show  cloudy 
swelling  and  other  degenerative  changes,  there  will  be 
some  leucocyte  infiltration,  and  the  ducts  will  be  dilated ; 
but  although  such  an  organ  may  during  life  be  distinctly 
enlarged  and  hardened,  after  death  it  may  appear  to  be 
normal  or  nearly  normal  to  the  naked  eye,  and  even 
microscopically  will  show  no  increase  of  fibrous  tissue. 

The  fact  that  obstruction  of  the  pancreatic  duct  with 
27 


Fi-. 


133- 


-Cirrhosis    of    the 
(X  ca  40). 


pancreas 


41 8       The  Pancreas:  Its  Surgery  and  Pathology 

damming  back  and  infection  of  the  secretion  gives  rise 
to  chronic  pancreatitis  has  already  been  mentioned.  In 
practice  this  is  by  far  the  most  common  cause  of  the 
disease,  and  it  is  found  to  be  due  in  most  cases  to  the 
lodgment  of  a  gall-stone  in  the  lower  portion  of  the  com- 
mon bile-duct.  The  reason  for  the  association  of  the  two 
conditions  is  obvious  when  the  anatomy  of  the  parts  is 
considered. 

The  common  bile-duct,  starting  by  the  junction  of  the 
cystic  duct  and  hepatic  duct,  courses  along  the  free  border 
of  the  lesser  omentum  associated  with  the  portal  vein  and 
hepatic  artery;  it  then  passes  behind  the  first  portion  of 
the  duodenum,  and  soon  comes  into  relation  with  the 
pancreas,  which  it  either  grooves  deeply,  or  passes  through 
or  behind,  before  it  pierces  the  wall  of  the  second  part  of 
the  duodenum,  where  it  empties  into  the  diverticulum  of 
Vater  along  with  the  duct  of  Wirsung.  It  may  be  divided 
into  four  portions:  (a)  The  supraduodenal  portion,  (6) 
the  retroduodenal  portion;  (c)  the  pancreatic  portion; 
(d)  the  intraparietal  portion. 

The  supraduodenal  and  the  retroduodenal  sections  of 
the  duct  are  unimportant  for  our  present  purpose,  but 
the  relations  of  the  pancreatic  and  the  intraparietal  por- 
tion of  the  duct  require  careful  consideration. 

The  fourth,  or  intraparietal,  segment  of  the  common 
duct  comprises  all  that  portion  of  the  canal  contained  in 
the  thickness  of  the  wall  of  the  duodenum.  It  passes 
obliquely  through  the  muscular  coat  of  the  intestine,  and 
then  dilates  into  a  little  reservoir  underneath  the  mucous 
membrane  into  which  the  main  pancreatic  duct  also 
opens,  known  as  the  ampulla  of  Vater.  The  ampulla 
opens  into  the  duodenum  by  a  little  round  or  elliptical 
orifice,  which  is  the  narrowest  part  of  the  bile-channel. 
The  mode  of  formation  of  the  ampulla  of  Vater  and  the 
termination  of  the  common  and  pancreatic  ducts  are 
liable  to  at  least  six  variations.     These  have  already  been 


Chronic  Pancreatitis  419 

considered  in  connection  with  the  anatomy  and  anatomi- 
cal abnormaUties  of  the  gland,  but  as  they  have  such  an 
important  bearing  on  the  subject  of  chronic  pancreatitis 
it  will  not  be  out  of  place  if  they  are  again  summarised 
here  in  this  connection. 

The  first  type  is  the  classical  one,  which  is  described 
above.  In  the  second  type  the  pancreatic  duct  joins  the 
common  duct  some  little  distance  from  the  duodenum,  the 
ampulla  of  Vater  is  absent,  and  the  duct  opens  into  the 
duodenum  by  a  small,  flat,  oval  orifice.  In  the  third 
type  the  two  ducts  open  into  a  small  fossa  in  the  wall  of 
the  duodenum,  while  the  caruncle  and  the  ampulla  of 
Vater  are  absent.  In  the  fourth  type  the  caruncle  is 
well  developed,  but  the  ampulla  is  absent,  the  two  ducts 
opening  side  by  side  at  the  apex  of  the  caruncle.  In  the 
fifth  type  the  common  bile-duct  opens  along  with  the 
duct  of  Santorini,  and  Wirsung's  duct  enters  the  duode- 
num separately.  In  the  sixth  type  the  pancreas  has 
three  separate  ducts  opening  into  the  duodenum,  one  only 
accompanying  the  common  bile-duct. 

It  will  be  seen  that,  while  the  normal  termination  and 
the  second  variety  of  termination  of  the  ducts  will  favour 
the  onset  of  pancreatitis  in  case  of  common-duct  chole- 
lithiasis, the  variations  3  and  4,  in  which  the  two  ducts  are 
separate,  will  possibly  save  the  patient  from  the  serious 
secondary  pancreatic  troubles,  and  in  variation  5  and  6  a 
small  portion  only  of  the  gland  will  become  infected. 

But  the  pancreatic  ducts  themselves  are  also  subject 
to  great  variations  that  may  influence  the  course  of  events. 
The  result  of  observations  by  Opie  on  100  cadavers  (Figs. 
30,  61)  in  which  the  ducts  were  injected  and  photo- 
graphed was  as  follows : 

In  ninety-nine  specimens  the  two  ducts  were  united; 
in  ten,  two  wholly  independent  ducts  entered  the  intes- 
tine. 


420       The  Pancreas:  Its  Surgery  and  Pathology 

1 .  Of  the  ducts  in  anastomosis : 

(i)  Duct  of  Wirsung  was  the  larger  in  eighty-four. 

(a)  Duct  of  Santorini  patent  in  sixty-three. 

(6)  Duct  of  Santorini  not  patent  in  twenty-one . 
(2)   Duct  of  Santorini  larger  in  six. 

(a)   Duct  of  Wirsung  patent  in  six. 

(6)   Duct  of  Wirsung  not  patent  in  any. 

2.  Ducts  not  in  anastomosis  in  ten. 

(a)  Duct  of  Wirsung  larger  in  five. 
(6)   Duct  of  Santorini  larger  in  five. 

In  89  per  cent,  the  duct  of  Wirsung  was  larger  than  the 
duct  of  Santorini,  while  in  2 1  per  cent,  the  duct  of  Santo- 
rini was  apparently  obliterated  near  its  termination. 
In  six  cases  the  duct  of  Santorini  was  larger  than  the 
duct  of  Wirsung.  In  all  cases  where  the  duct  of  Santorini 
was  patent  it  diminished  in  size  towards  the  duodenum. 
Thus  the  duct  of  Santorini  cannot  be  relied  on  in  many 
cases  to  supplement  the  duct  of  W-irsung,  if  it  be  ob- 
structed ;  moreover,  the  duct  of  Santorini,  even  if  patent 
and  communicating  with  the  duodenum,  may  itself  be 
compressed  by  a  moderate-sized  gall-stone  passing  down 
the  pancreatic  portion  of  the  common  duct. 

It  might  be  argued  that  if  the  two  ducts  communicate, 
why  should  not  the  duct  of  Santorini  act  as  a  safety-valve 
to  the  duct  of  Wirsung  when  it  is  compressed,  and  thus 
free  the  pancreas  from  the  retained  secretion,  which  is  in 
danger  of  becoming  septic?  It  will  be  seen  that  in  only 
half  or  less  than  half  of  all  cases  will  the  duct  of  Santorini 
act  as  a  safety-valve  if  the  duct  of  Wirsung  is  obstructed, 
for  although  in  63  per  cent,  of  cases  the  duct  opens  at  the 
same  time  into  the  main  channel  and  into  the  intestines, 
yet  in  probably  less  than  half  of  these  is  the  anastomosis 
efficient  as  a  through  channel. 

The  reasons  why  gall-stones  in  the  common  bile-duct 
do  not  always  produce  pancreatic  inflammation  are: 

(a)  Some   gall-stones    are    so   large   that   they   never 


Chronic  Pancreatitis  -421 

reach  the  pancreatic  portion  of  the  duct,  but  remain  in 
the  supraduodenal  portions  of  the  common  duct,  pro- 
ducing jaundice  but  no  pancreatitis. 

(b)  In  some  cases  the  bile-ducts  and  pancreatic  ducts 
open  by  separate  orifices,  and  any  gall-stone  passing  down 
the  common  duct  will  not  then  necessarily  compress  or 
occlude  the  pancreatic  duct, 

(c)  In  exceptional  cases  the  duct  of  Santorini  is  the 
principal  outlet  for  the  pancreatic  fluid,  it  being  of  such 
a  size  as  to  affor^"!  a  safe  outlet  to  the  secretion  even  when 
the  duct  of  Wirsung  is  obstructed. 

The  course  of  the  third  or  pancreatic  portion  of  the 
common  duct  is  also  of  great  interest,  for  if  it  passes  through 
the  gland,  any  congestion  or  swelling  of  the  head  of  the 
pancreas  will,  by  the  pressure  it  exerts  on  the  common 
duct,  tend  to  induce  jaundice  and  its  various  sequelae; 
whereas  if  it  passes  behind,  and  not  through,  the  head  of 
the  gland,  it  will  escape  from  pressure  when  the  pancreas 
is  inflamed. 

The  passage  of  the  common  duct  through  the  substance 
of  the  pancreas  in  a  certain  proportion  of  individuals 
probably  explains  many  of  the  cases  of  so-called  catarrhal 
jaundice,  which  may  come  on  as  an  extension  from  gastro- 
duodenal  catarrh,  or  in  the  course  of  various  ailments, 
and  which  it  is  not  unlikely  are  often  dependent  on  catar- 
rhal inflammation  and  swelling  of  the  pancreas,  leading 
to  pressure  on  the  bile-ducts.  Such  are  many  of  the  cases 
of  acute  jaundice,  especially  the  form  coming  on  in  young 
subjects,  and  which  usually  clear  up  under  medical  treat- 
ment. They  are  truly  pancreatic  and  not  biliary  in 
origin,  and  some  of  these  cases  pass  on  from  the  simple 
'congestive  or  catarrhal  form  to  true  interstitial  pancreat- 
itis. The  so-called  chronic  catarrh  of  the  bile-ducts  lead- 
ing to  persistent  jaundice  is  nearly  always  due  to  chronic 
pancreatitis,  the  obstruction  to  the  flow  being  outside  and 
not  inside  the  common  duct. 


422       The  Pancreas:  Its  Surgery  and  Pathology 

As  the  duct  is  completely  embraced  by  the  pancreas  in 
62  per  cent,  of  all  cases,  we  may  conclude  that  in  about 
that  proportion  of  cases  a  swelling  of  the  head  of  the  pan- 
creas will  produce  jaundice,  and,  as  supporting  this  view, 
this  percentage  corresponds  with  our  clinical  and  path- 
ological investigations  of  the  urine  of  pancreatic  cases, 
when  associated  with  gall-stones  in  the  common  bile- 
duct. 

A  gall-stone  passing  down  a  duct  thus  embraced  by  the 
pancreas  is  almost  certain  to  exert  pressure  on  the  gland, 
and  the  resulting  inflammatory  changes  may  in  their  turn 
give  rise  to  compression  of  the  duct,  which  will  result  in 
jaundice  that  may  persist  long  after  the  gall-stone  itself 
has  passed. 

Occasionally  the  ducts  are  obstructed  by  other  causes 
than  gall-stones.  A  growth  occurring  in  the  ampulla  of 
Vater,  or  in  the  papilla,  will  interfere  with  the  free  flow 
of  the  pancreatic  secretion,  and  may  give  rise  to  catarrh 
of  the  ducts  and  chronic  pancreatitis.  An  impacted  pan- 
creatic calculus,  or  stenosis  of  the  duodenal  opening  of  the 
duct  following  ulceration,  will  also  produce  a  similar 
result ;  and  recently  a  case  has  been  reported  in  which  a 
portion  of  hydatid  membrane  was  the  oostructing  agent. 

How  far  the  pancreatic  lesion  in  these  obstruction 
cases  is  to  be  attributed  to  the  irritating  action  of  the 
retained  secretion,  and  how  far  to  the  associated  bacterial 
infection,  is  difficult  to  say,  but  it  is  probable  that  in  all 
cases  the  latter  plays  an  important  part.  Even  when 
the  blocking  of  the  ducts  is  complete,  and  no  direct  com- 
munication between  the  micro-organisms  in  the  duodenum 
and  the  stagnant  secretion  appears  to  be  possible,  the 
inflamed  walls  of  the  duct  present  a  ready  path  for  the 
passage  of  infection.  This  has  been  proved  in  the  bile- 
passages  by  aseptic  ligature  of  the  common  duct.  Abso- 
lutely complete  blocking  of  the  duct  is,  however,  very 
uncommon,  except  in  cancer  cases,  for  bile-pigment  can 


Chronic  Pancreatitis  423 

be  found  chemically  in  the  faeces  in  nearly  all  other  cases, 
even  when  the  stools  are  free  from  colour  to  the  naked  eye. 

Chronic  pancreatitis  may  result  from  a  direct  exten- 
sion of  a  duodenal  catarrh  to  the  pancreatic  ducts,  and 
this  association  of  chronic  pancreatitis  with  duodenal 
catarrh  is  not  at  all  uncommon.  It  has  been  shown 
experimentally  that  by  injecting  fsecal  material  or  bacil- 
lus coli  into  the  pancreatic  ducts,  or  by  providing  a  chan- 
nel, such  as  an  absorbent  thread,  by  which  organisms 
may  enter  from  the  bowel,  pancreatitis  is  produced; 
and  that  after  some  time  the  gland,  which  is  constantly 
being  infected  by  a  permanent  channel,  eventually  be- 
comes sclerosed.  We  have  had  the  opportunity  of  inves- 
tigating a  considerable  number  of  cases  in  which  pancrea- 
titis has  followed  chronic  gastric  or  gastro-intestinal 
catarrh  and  duodenal  ulcer,  and  in  many  of  them  the 
condition  has  been  relieved  by  operation. 

The  pancreatitis  which  is  occasionally  met  with  as  a 
sequel  of  typhoid  fever  is  probably  due  to  a  specific 
infection  occurring  in  a  similar  way,  though  infection  by 
way  of  the  blood  and  changes  due  to  toxaemia  cannot  be 
excluded.  In  support  of  this  hypothesis  is  the  fact  that 
typhoid  bacilli  have  been  recovered  from  the  bile  in  the 
common  duct  and  gall-bladder  in  some  cases  where 
operation  has  been  undertaken. 

Influenza  and  some  other  zymotic  diseases  are  also 
occasionally  followed  by  inflammation  of  the  pancreas. 
In  these  cases  infection  may  take  place  by  way  of  the  duo- 
denum, or  possibly  through  the  blood. 

The  chronic  infections,  tubercle  and  syphilis,  may  also 
give  rise  to  pancreatitis.  In  the  former  chronic  inflam- 
matory changes  may  be  found  in  the  absence  of  definite 
tuberculous  deposits,  and  the  experiments  of  Carnot  with 
tubercle  bacilli  and  tuberculin  in  dogs  suggest  that  the 
changes  are  due  to  toxic  substances  circulating  in  the 
blood,  rather  than  to  the  direct  effect  of  the  bacillus  in 


424      The  Pancreas:  Its  Surgery  and  Pathology 


the   gland.     It   is   probable   that   syphilitic  pancreatitis 
is  a  similar  toxic  manifestation. 

The  influence  of  alcoholism  in  the  production  of  cirrho- 
sis of  the  liver  is  still  a  debatable  point,  and  similarly  its 
relation  to  chronic  pancreatitis  has  not  been  settled. 
In  some  cases  a  history  of  alcoholic  excess  can  be  obtained, 
but  in  many  this  is  not  so.  It  is  probable  that  alcohol  is 
not  of  itself  a  direct  determining  cause,  but  that  indirectly, 
by  the  influence  it  exerts  on  the  circulation  and  by  the 

production  of  a  catarrh  of  the 
duodenum,  it  may  give  rise  to 
pancreatitis. 

Chronic  pancreatitis  and 
cirrhosis  of  the  liver  are  not 
infrequently  associated.  Ac- 
cording to  the  observations 
of  Lefas  and  Opie,  chronic 
pancreatitis  may  accompany 
either  atrophic  or  hypertro- 
phic cirrhosis,  but  while  in 
the  former  the  gland  is  en- 
larged and  the  newly  formed 
fibrous  tissue  interacinar  in 
distribution,  in  the  latter  no 
marked  increase  of  size  takes 
place,  and  it  is  the  interlob- 
ular tissue  that  is  increased  in 
amount  and  density.  It  is  not  uncommon  to  find  both 
diseases  present  in  long-continued  obstruction  of  the 
common  duct  by  gall-stones. 

In  that  peculiar  condition  hcemochromatosis,  the  pan- 
creas is  affected,  and  chronic  interacinar  pancreatitis 
folows  the  deposit  of  pigment  and  associated  atrophy  of 
the  gland  cells. 

As  in  the  kidney  and  other  organs,  an  increase  of  fibrous 
tissue  occurs  in  the  pancreas  in  general  arteriosclerosis 


Fig.  134.— Chronic  ulcer  of 
the  posterior  wall  of  the  stom- 
ach eroding  the  pancreas  (R. 
C.  S.  Museum  2399). 


Chronic  Pancreatitis 


425 


rlJ-^ 


?^^*«^ 


Fig.  135. — Section  of  the  pancreas 
in  the  neighbourhood  of  p,n  adherent 
gastric  ulcer,  showing  the  secondary 
interstitial  pancreatitis  (X  40). 


and  endarteritis,   and  it  is  possible  that  the  moderate 

increase  found  micro- 
scopically in  a  certain 

number  (10  per  cent. 

of  Bosanquet's  cases) 

of  patients  over  forty 

years  of  age  may  be 

attributed    to     this 

cause,  but  that  it  is 

not  a  common  cause 

is    shown   by    Opie's 

investigations. 

Occasionally     one 

meets    with    chronic 

pancreatitis    due    to 

direct     extension    of 

the    inflammatory 

process  from  a  neigh- 
bouring organ,    such  as  a  chronic  gastric  ulcer  eroding 

the  gland. 

A  malignant 
growth  of  the  py- 
lorus may  set  up 
perigastritis  and 
cause  the  stomach 
to  become  adher- 
ent to  the  pancreas, 
producing  well- 
marked  interstitial 
pancreatitis  in  the 
head  of  the  gland, 
as  in  a  case  oper- 
ated on  by  one  of 
us  recently. 

Acute      or    sub- 
acute inflammation  of  the  pancreas,  if  not  ending  fatally. 


Fig.  136. 


-Chronic   suppurative  pancreati- 
tis (X  ca  35). 


426       The  Pancreas:  Its  Surgery  and  Pathology 

may  resolve  and  be  succeeded  by  chronic  inflammatory 
changes  that  may  ultimately  lead  to  cirrhosis  and  to  a 
fatal  termination  at  a  later  date,  as  was  demonstrated  in 
one  of  our  cases  of  abscess  of  the  pancreas  that  died  three 
months  after  operation,  in  which  an  opportunity  occurred 
of  examining  the  gland  microscopically. 

In  cystic  disease  of  the  pancreas,  chronic  pancreatitis 
is  nearly  always  present ;  in  fact,  it  is  probably  the  com- 
pression of  the  smaller  duct  by  the  contracting  newly 
formed  fibrous  tissue  that  in  many  cases  gives  rise  to  the 
cysts. 

All  the  causes  of  chronic  pancreatitis  mentioned, 
except  atrophic  cirrhosis  and  ha^mochromatosis,  are  asso- 
ciated with  interlobular  changes  in  the  fibrous  tissue,  and 
from  a  surgical  point  of  view  this  is  the  most  important 
form  of  chronic  inflammxation  to  which  the  gland  is  liable, 
for  it  is  capable  of  being  distinctly  benefited  by  operative 
interference,  if  recognized  at  a  sufficiently  early  stage. 

The  etiology  of  the  interacinar  variety  is  at .  present 
for  the  most  part  obscure,  although,  judging  from  the 
early  stages  at  which  the  islands  of  Langerhans  are  affected 
and  the  centrifugal  character  of  the  new  fibrous  tissue 
formation,  it  is  probable  that  the  disease  owes  its  origin 
to  an  abnormal  state  of  the  blood.  It  is  therefore  not 
likely  to  prove  directly  amenable  to  surgical  treatment. 

Symptomatology. — The  onset  of  chronic  pancreatitis 
varies  with  the  cause.  If  it  is  due  to  obstruction  of  the 
common  duct  by  a  gall-stone,  there  will  be  a  history  of 
painful  attacks  in  the  right  hypochondrium  and  in  the 
epigastrium,  associated  with  jaundice  and  possibly  accom- 
panied by  fever  of  an  intermittent  type.  Tenderness  at 
the  epigastrium,  with  some  fulness  above  the  umbilicus, 
will  usually  be  noticed ;  loss  of  flesh  soon  becomes  marked, 
and  if  the  pancreatic  symptoms  predominate,  the  pain 
will  pass  from  the  epigastrium  round  the  left  side  even  to 
the  renal  and  scapular  regions. 


Chronic  Pancreatitis  427 

If,  however,  the  condition  arises  by  direct  infection 
from  a  duodenal  catarrh  or  from  one  of  the  other  causes 
mentioned,  and  not  connected  with  choleHthiasis,  there 
may  be  merely  an  aching  in  the  epigastrium  or  slight  pain 
not  at  all  pronounced,  or  the  symptoms  may  come  on 
painlessly,  associated  with  dyspepsia  and  with  slight 
jaundice,  soon  becoming  more  marked;  in  such  cases  the 
gall-bladder  may  dilate  and  give  rise  to  a  suspicion  of 
cancer  of  the  pancreas  which  the  rapid  loss  of  flesh  will 
tend  to  confirm.  In  either  case  a  train  of  symptoms  of  a 
very  definite  character  is  set  up,  and  it  is  difficult  to  un- 
derstand how  the  idea  has  gained  currency  that  chronic 
pancreatitis  is,  as  a  rule,  undiagnosable  during  life. 

Physical  examination  of  the  patient  will  reveal  in 
some  few  cases  a  swelling  of  the  pancreas  due  to  tumefac- 
tion of  the  head  of  the  gland ;  but  as  the  recti  are  often 
rigid  from  the  pain  and  tenderness  in  the  epigastrium,  it 
may  be  discoverable  only  when  the  patient  is  anaesthe- 
tised. . 

Pain  and  tenderness,  though  usually  present,  may  be 
little  marked,  but  in  some  cases  the  pain  is  paroxysmal 
and  severe,  and  epigastric  tenderness  is  well  pronounced. 
By  distending  the  stomach  with  gas,  either  by  means  of 
carbonate  of  soda  and  tartaric  acid  given  in  separate 
doses,  or  by  pumping  in  air  through  the  stomach-tube, 
the  relation  of  the  stomach  to  the  swelling  can  be  readily 
made  out.  Resonance  on  percussion,  owing  to  the  posi- 
tion of  the  stomach,  unless  the  stomach  is  empty,  com- 
municated non-expansile  pulsation,  and  very  slight  move- 
ment on  deep  inspiration  are  characteristic. 

In  the  more  chronic  stages,  especially  when  the  disease 
has  reached  the  cirrhotic  stage,  if  the  cause  be  not  gall- 
stones, a  tumour  of  the  gall-bladder  is  found  similar  to 
that  met  with  in  cancer  of  the  pancreas.  The  distension 
is  due  to  mucus,  the  bile  which  first  filled  it  having  been 
absorbed  and  the  backward  pressure  having  prevented 


428       The  Pancreas:  Its  Surgery  and  Pathology 

fresh  bile  from  entering  the  duct.  The  distension  may 
occur  so  gradually  as  to  be  painless,  and  the  gall-bladder 
is  then  free  from  tenderness,  which  is  less  frequently 
the  case  in  distension  due  to  gall-stones.  In  jaundice 
due  to  a  stone  in  the  common  duct  the  gall-bladder  is 
nearly  always  contracted  and  not  capable  of  being  felt. 

Jaundice  is  not  necessarily  present  at  first,  although 
it  is  usually  met  with  at  some  stage  of  the  disease,  and  is 
often  well  marked.  It  may  vary  from  a  slight  icteric 
tinge,  most  marked  in  the  sclerotics,  to  an  intense  mahog- 
any hue.  In  chronic  pancreatitis,  due  to  obstruction  of 
the  common  bile-duct  by  a  gall-stone,  the  jaundice  is 
frequently  very  marked,  as  it  is  also  in  those  cases  where 
the  duct  passing  through,  or  grooving,  the  head  of  the 
pancreas  is  compressed  by  the  swollen  gland ;  when,  how- 
ever, the  common  bile-duct  passes  behind  the  gland,  as  it 
does  in  38  per  cent,  of  bodies,  the  patency  of  the  passage 
may  not  be  seriously  interfered  with  and  little  or  no  jaun- 
dice be  produced.  An  increase  of  temperature  is,  as  a 
rule,  associated  with  acute  and  subacute  pancreatitis, 
but  only  rarely  in  any  of  the  more  chronic  forms  of  inflam- 
mation, except  in  those  cases  where  there  is  associated 
infective  cholangitis,  as  in  obstruction  of  the  common 
duct  by  a  biliary  calculus  and  infection  of  the  retained 
secretion,  when  there  may  be  fever  of  an  intermittent 
type  and  ague-like  paroxysms. 

Dyspeptic  disturbances  are  constantly  complained  of; 
they  take  the  form  of  anorexia  with  discomfort  from  flat- 
ulency, sometimes  offensive  eructations,  heartburn,  nausea, 
distaste  for  fats  and  for  meat.  Frequent,  bulky  motions, 
pale  in  colour,  offensive,  and  obviously  greasy,  are  usually 
present  in  advanced  conditions,  though  in  the  earlier 
stages  there  maybe  constipation  associated  with  flatulency. 
Marked  and  often  excessive  wasting  is  often  a  prominent 
symptom. 

The  urine  will  give  a  more  or  less  well-marked  pan- 


Chronic  Pancreatitis  429 

creatic  reaction  according  to  the  extent  and  intensity  of 
the  lesion,  and  a  quantitative  chemical  analysis  of  the 
fasces  will  show  an  excess  of  unabsorbed  fat,  of  which 
the  greater  part  is  unsaponified  "neutral  fat,"  particu- 
larly if  there  are  advanced  interstitial  changes  in  the 
gland. 

Although  in  any  single  case  we  may  not  have  all  the 
symptoms  and  signs,  yet  in  no  case  ought  we  to  fail  to 
find  evidence  of  digestive,  metabolic,  or  physical  signs 
if  chronic  inflammation  of  the  pancreas  be  present. 

No  single  symptom  can  alone  be  relied  upon  as  diagnos- 
tic of  chronic  pancreatitis,  but  on  considering  all  the 
available  evidence  there  is  not  usually  much  difficulty 
in  forming  an  opinion.  Special  stress  can  be  laid  upon 
the  progressive  wasting,  the  usual  presence  of  jaundice, 
the  dyspeptic  disturbances,  the  pancreatic  reaction  in  the 
urine,  and  the  results  of  the  chemical  examination  of  the 
faeces.  Each  case,  however,  has  to  be  considered  on  its 
merits,  and  in  making  the  diagnosis  one  has  to  bear  in 
mind  the  difference  in  the  symptoms  produced  by  the 
various  causes  as  well  as  by  the  variations  in  the  anatomy 
of  the  ducts. 

In  the  differential  diagnosis  of  chronic  pancreatitis 
the  most  important  conditions  to  consider  are  cancer  of 
the  head  of  the  pancreas,  cancer  of  the  common  bile-duct, 
cancer  of  the  liver,  gall-stones  in  the  common  duct,  and 
chronic  catarrh  of  the  bile-ducts. 

In  cancer  of  the  head  of  the  pancreas  the  onset  is 
usually  gradual  and  painless,  and  the  disease  usually 
occurs  later  in  life,  generally  after  forty  years  of  age.  It 
is  preceded  by  general  failure  of  health,  and  when  jaun- 
dice supervenes  it  becomes  absolute  and  unvarying.  The 
gall-bladder  is  nearly  always  distended,  and  may  attain  a 
large  size.  It  is  not  tender  on  manipulation.  The  liver 
enlarges  from  biliary  stasis,  but  there  are  no  nodules  to 
be  felt.     In  some  rare  cases  a  hard  nodular  tumour  may 


430       The  Pancreas:  Its  Surgery  and  Pathology 

be  felt  on  the  inner  side  of  the  distended  gall-bladder. 
The  fasces  are  usually  acid  in  reaction,  and  contain  a  large 
amount  of  undigested  fat,  only  a  comparatively  small  pro- 
portion of  which  consists  of  fatty  acids.  The  pancreatic 
reaction  in  the  urine  is  negative  by  the  improved  method  in 
about  7  5  per  cent,  of  cases,  but  in  the  remaining  2  5  per  cent, 
a  more  or  less  marked  reaction,  probably  due  to  the  asso- 
ciated inflammatory  changes,  is  obtained.  Preparations 
made  by  the  original  A-reaction  show  coarse  crystals, 
soluble  in  33  per  cent,  sulphuric  acid  in  three  to  five  min- 
utes, in  many  cases,  but  a  typical  reaction  is  not  easily 
obtained  and  it  may  be  necessary  to  make  several  prepara- 
tions from  more  than  one  specimen  of  urine  before  they 
are  secured.  The  extremely  rapid  loss  of  weight  and 
strength  with  increasing  ansemia,  but  without  ague -like 
seizures,  is  very  characteristic,  and  it  is  common  for  there 
to  be  an  absence  of  fever,  or  indeed  a  subnormal  tempera- 
ture, with  a  slow  feeble  pulse,  and  later  ascites  with  oedema 
of  the  lower  limbs.  The  great  importance  of  an  accurate 
diagnosis  between  cancer  of  the  head  of  the  pancreas  and 
chronic  pancreatitis  lies  in  the  fact  that  while  the  latter 
is  eminently  a  curable  disease  when  submitted  to  early 
operation,  the  former  is  not  benefited  by  surgical  treat- 
ment, which,  moreover,  is  attended  by  no  little  danger 
from  various  complications. 

Cancer  of  the  comimon  duct  is  rare  and  is  usually  asso- 
ciated with  gall-stones.  If  the  disease  involves  the  pap- 
illa, the  symptoms  are  indistinguishable  from  those  of 
cancer  of  the  head  of  the  pancreas,  except  that  the  urinary 
pancreatic  reaction  is  more  likely  to  be  of  the  inflamma- 
torv  type  from  the  associated  changes  in  the  gland  due 
to  the  damming  back  of  its  secretion.  If  the  growth  is 
situated  above  the  opening  of  the  pancreatic  duct,  it  will 
not  interfere  with  the  functions  of  the  pancreas ;  the  loss 
of  flesh  will  not  be  so  rapid,  the  typical  pancreatic  reac- 
tion in  the  urine  will  be  absent,  and  although  there  may  be 


Chronic  Pancreatitis  431 

an  excess  of  fat  in  the  fseces,  this  will  consist  chiefly  of 
combined  fatty  acids. 

Cancer  of  the  liver  is  distinguished  by  the  irregular 
enlargement  and  nodular  feel  of  the  organ,  the  rapid  de- 
terioration of  health,  the  less  intense  jaundice,  and  the 
absence  of  fever  and  paroxysmal  pain.  The  pancreatic 
reaction  is  negative. 

A  diagnosis  of  gall-stones  may  be  made  by  the  sequence 
of  a  long  antecedent  history  of  spasms  without  jaundice, 
then  a  severe  attack  of  pain  followed  by  jaundice,  and 
after  a  time  recurrent  pains  with  increase  of  icterus  asso- 
ciated with  ague-like  seizures.  The  absence  of  tumour 
is  more  common  in  gall-stones  than  in  chronic  pancreatitis, 
though  in  the  latter  the  gall-bladder  may  be  found  con- 
tracted at  times.  The  paroxysmal  attacks  in  chronic 
pancreatitis  may  be  equally  as  severe  as  those  in  gall-stone 
seizures,  but  there  is  usually  less  pain.  The  tenderness, 
however,  with  gall-stones  will  be  over  the  gall-bladder, 
and  in  pancreatitis  at  the  middle  line  where  the  swollen 
gland  can  sometimes  be  felt,  especially  if  the  patient  is 
thin  or  under  the  influence  of  an  anaesthetic ;  moreover,  the 
radiating  pain  in  gall-stones  is  towards  the  right  infra- 
scapular  region,  and  in  pancreatitis  towards  the  left  or 
to  the  mid-scapular  region.  When  the  gall-stones  are 
situated  in  the  first  or  second  part  of  the  common  duct,  the 
pancreatic  reaction  is  negative  and  the  faeces  alkaline  in 
reaction.  The  motions,  although  often  containing  a  con- 
siderable excess  of  fat,  do  not  show  the  high  proportion  of 
neutral  fat  usually  found  in  pancreatic  cases,  but  are,  as  a 
rule,  rich  in  combined  fatty  acids.  When,  however,  a  stone 
is  impacted  in  the  third  part  of  the  duct,  there  is  a  proba- 
bility that,  in  the  majority  of  cases,  the  pancreas  will  be 
inflamed;  and  when  the  calculus  lies  in  the  fourth  part, 
the  pancreas  is  almost  certain  to  be  affected.  The  diag- 
nosis of  chronic  pancreatitis  from  gall-stones  is,  however, 
not  one  of  any  great  practical  importance,  since  the  two 


432       The  Pancreas:  Its  Surgery  and  Pathology 

conditions  are  often  associated,  and  the  treatment  is, 
at  least  up  to  a  certain  point,  the  same. 

Chronic  catarrh  of  the  bile-ducts  is  characterised  by 
jaundice  and  loss  of  flesh,  coming  on  for  the  most  part 
painlessly,  but  since  it  is  usually  of  pancreatic  origin, 
it  is  not  necessary  to  spend  time  in  discussing  it  further. 

Although  the  diseases  mentioned  are  the  most  likely 
to  cause  confusion  in  diagnosis,  they  are  not  by  any  means 
the  only  ones  for  which  chronic  pancreatitis  may  be  mis- 
taken. More  than  one  patient  has  been  sent  to  us  who, 
from  his  colour  and  recurrent  rigors,  had  been  believed  to 
be  suffering  from  ague.  The  absence  of  malaria  organ- 
isms in  the  blood,  the  presence  of  the  pancreatic  reaction 
in  the  urine,  a  chemical  examination  of  the  faeces,  and  a 
careful  consideration  of  all  the  physical  signs  and  symp- 
toms, have  quickly  revealed  the  true  condition  of  things, 
which  has  been  confirmed  by  operation  and  the  subsequent 
course  of  the  case. 

The  blood  changes  met  with  in  chronic  pancreatitis 
suggesting  pernicious  anaemia  have,  in  some  instances,  led 
to  an  incorrect  view  of  the  case  being  taken,  until  the 
possibility  of  their  being  of  pancreatic  origin  was  pointed 
out. 

Analysis  of  the  urine  and  faeces  by  one  of  us  in  several 
cases  diagnosed  by  various  authorities  as  "hill  diarrhoea, 
psilosis  or  sprue"  has  given  results  that  have  pointed  to 
the  pancreas  being  involved  in  the  disease,  and  in  one 
case  that  was  operated  on  and  a  cholecystenterostomy 
performed  the  condition  of  the  patient  was  much  inproved . 
The  faeces  in  this  case  before  the  operation  contained  62 
per  cent,  of  total  fat,  of  which  41  per  cent,  was  neutral 
fat  and  21  per  cent,  combined  fatty  acid.  The  urine  gave 
a  well-marked  and  characteristic  "pancreatic  reaction." 
After  the  operation  the  patient  put  on  flesh,  his  appetite 
improved,  and  at  the  end  of  a  month  the  fasces  were  found 
to  contain  45  per  cent,  of  total  fat,  29  per  cent,  of  neutral 


Chronic  Pancreatitis  433 

fat,  and  the  same  amount  of  combined  fatty  acid  as  before, 
namely,  21  per  cent.  There  was  thus  not  only  a  dimin- 
ished amount  of  fat  in  the  stools,  but  there  was  also  a 
much  lower  percentage  of  this  in  an  undigested  form. 
His  general  health  had  continued  good  nine  months  after 
the  operation,  and  he  then  stated  that,  save  for  an  occa- 
sional relapse  which  generally  results  from  some  error  in 
diet,  he  had  been  free  from  pain  and  the  faeces  had  been 
more  nearly  normal  than  for  several  years  previously. 
A  specimen  of  faeces  examined  during  one  of  the  relapses 
showed  60  per  cent,  of  fat,  of  which  42  per  cent,  was  neu- 
tral fat  and  18  per  cent,  combined  fatty  acid.  The  pan- 
creatic element  in  at  least  some  cases  having  the  symp- 
toms of  sprue  has  not,  we  believe,  been  previously  insisted 
upon,  but  it  is,  we  think,  a  point  that  should  be  borne 
in  mind  in  the    diagnosis  and  treatment  of  the  disease. 

The  prognosis  of  chronic  interstitial  pancreatitis  surgi- 
cally treated  is  very  favourable,  but  the  longer  the  disease 
is  left  untreated,  the  more  serious  the  outlook  becomes. 
In  some  cases  it  may  slowly  progress  for  months  or  even 
years,  but  ultimately  the  well-marked  cases  die,  either 
from  asthenia  or  more  rarely  from  haemorrhage  or  dia- 
betes. A  marked  haemorrhagic  tendency  usually  shows 
the  near  approach  of  a  fatal  termination,  and  when  dia- 
betes has  supervened,  the  disease  is,  as  a  rule,  so  far  ad- 
vanced that  surgical  interference  is  not  likely  to  do  more 
than  possibly  delay  its  progress,  though  a  moderate  degree 
of  glycosuria  need  not  be  a  bar  to  operation,  as  this  may 
arrest  the  progress  of  the  disease. 

Treatment. — Before  considering  either  the  medical  or 
surgical  treatment  of  pancreatitis,  the  importance  of  pre- 
ventive treatment  by  attention  to  the  causes,  some  of 
which,  such  as  gall-stones,  are  removable  by  operation  in 
the  very  early  stages  with  a  very  small  risk,  certainly 
not  more  than  i  per  cent,  in  skilful. hands,  must  be  in- 
sisted upon.  Duodenal  catarrh  as  a  cause  of  pancreatic 
28 


434       The  Pancreas:  Its  Surgery  and  Pathology 

catarrh  and  of  interstitial  pancreatitis  is  remediable  by 
medical  treatment;  and  duodenal  ulcer,  another  cause, 
if  not  remedied  by  careful  and  thorough  general  treat- 
ment, can  be  cured  by  gastro-enterostomy  with  a  very 
small  risk. 

If,  after  a  fair  trial  of  general  treatment,  care  in  diet, 
wet  packs  to  the  epigastrium,  rest,  and  mild  mercurial 
purges,  not  too  long  continued,  the  symptoms  persist, 
and  the  signs  of  failure  in  pancreatic  digestion  and  metab- 
olism are  manifesting  themselves,  the  question  of  sur- 
gical treatment  should  be  seriously  considered,  especially 
when  the  disease  is  associated  with  jaundice,  for  the 
condition  is  one  that,  if  not  relieved  early,  will  certainly 
lead  to  serious  degeneration  of  both  the  liver  and  pan- 
creas, and  become  dangerous  to  life  in  several  ways. 

Rational  treatment  should  aim  at  the  cause,  whether 
that  be  gall-stones,  pancreatic  calculi,  duodenal  catarrh, 
duodenal  or  gastric  ulcer,  alcoholism,  or  syphilis. 

In  operating  for  chronic  pancreatitis  when  medical 
treatment  has  failed  to  relieve,  the  surgeon  must  be  pre- 
pared to  do  a  thorough  operation,  so  as  to  expose  the 
whole  length  of  the  common  bile-duct  as  well  as  the  head 
of  the  pancreas.  He  will  then  be  able  to  remove  the  cause 
should  it  prove  to  be  a  gall-stone,  or  a  pancreatic  calculus, 
or  any  other  removable  condition.  In  the  absence  of 
some  obvious  removable  cause,  it  is  advisable  to  secure 
efficient  drainage  of  the  infected  bile-duct  and  pancreatic 
duct,  either  by  cholecystotomy  or  cholecystenterostomy, 
preferably  the  latter.  Where  the  pancreatic  disease  is 
dependent  on  duodenal  catarrh  associated  with  ulcer  of 
the  duodenum,  it  may  be  advisable,  at  the  same  time  that 
the  bile-passages  are  drained,  to  perform  also  a  gastro- 
enterostomy in  order  to  cure  the  original  cause  of  the 
disease.  Experience  has  taught  that  if  the  cause  can  be 
removed  at  an  early  stage,  an  absolute  cure  is  possible ; 
and  though  complete  restoration  of  the  damaged  gland 


Chronic  Pancreatitis  435 

in  more  advanced  cases  cannot  always  be  promised,  yet 
an  arrest  of  the  morbid  process  may  be  looked  for,  and 
the  remaining  portion  of  the  pancreas  will  be  able  to 
carry  on  the  metabolic,  and,  even  if  incompletely,  the 
digestive  functions  of  the  gland. 

Surgical  Treatment. — In  several  of  our  earlier  cases  of 
chronic  pancreatitis  the  abdomen  was  opened  and  the 
biliary  ducts  and  swollen  head  of  the  pancreas  were 
exposed  and  manipulated  without  finding  gall-stones. 
Whether  it  was  that  the  manipulation  of  the  parts  dis- 
placed and  pushed  on  a  stone  from  the  common  duct  into 
the  duodenum,  or  that  the  breaking  down  of  adhesions 
relieved  tension,  the  fact  remains  that  in  a  number  of 
such  cases  the  patients  completely  recovered  and  re- 
mained well.  This  was  the  course  of  events  in  the  follow- 
ing case : 

The  patient,  a  woman,  aged  forty-four  years,  had  for 
some  time  been  suffering  from  deep  jaundice  with  con- 
siderable pain,  some  irregular  fever,  digestive  disturbance, 
and  emaciation.  At  the  operation  on  June  22,  1890, 
after  separating  a  number  of  adhesions,  a  tumour  of  the 
pancreas  embracing  the  lower  end  of  the  common  duct 
was  found,  which  at  the  time  was  thought  to  be  malignant. 
The  tumour  was  freely  manipulated  in  order  to  ascertain 
if  any  gall-stones  were  present  in  the  common  duct,  but 
none  could  be  felt,  and  as  the  gall-bladder  was  contracted 
and  there  was  some  tendency  to  heemorrhage  from  numer- 
ous small  points,  the  investigation  was  not  carried  further 
and  the  abdomen  was  closed.  Whether  any  concretion 
was  pressed  onward  into  the  duodenum  it  is  impossible 
to  say,  but  the  patient  made  a  good  recovery  from  the 
operation  and  within  a  few  months  she  had  regained  her 
health.  A  letter  received  from  her  medical  man  states 
that  she  is  now,  fourteen  years  afterwards,  in  very  good 
health. 

But  in  other  cases  of  this  kind,  although  the  patients 
have  recovered  from  operation  and  apparently  become 
restored  to  health,   an  examination  of  the  urine  years 


436       The  Pancreas:  Its  Surgery  and  Pathology 

later  has  shewn  the  presence  of  the  pancreatic  reaction, 
and  in  some  cases  there  has  been  glycosuria  due  to  a 
seriously  damaged  pancreas.  The  following  is  a  case  in 
point : 

Mr.  D ,  aged  forty-two,  had  an  attack  of  pain  in 

the  right  hypochondrium  ten  years  ago,  but  no  jaundice. 
He  had  been  free  from  attacks  up  to  six  weeks  before 
seeing  one  of  us,  when  he  had  a  severe  attack  of  pain  in. 
the  right  hypochondrium,  radiating  to  the  back  and 
shoulders,  accompanied  by  rigors  and  vomiting  and  fol- 
lowed, by  jaundice.  The  jaundice  had  persisted  up  to 
the  time  of  his  being  seen,  but  then  no  swelling  could  be 
felt.  An  exploratory  operation  was  performed  on  Octo- 
ber 27,  1898,  when  a  mass,  thought  to  be  growth  in  the 
head  of  the  pancreas,  was  discovered.  The  patient  made 
a  good  recovery  with  gradual  relief  to  the  jaundice.  The 
enlargement  of  the  head  of  the  pancreas  was  doubtless 
chronic  pancreatitis,  as  it  was  too  soft  for  scirrhus.  It 
was  very  freely  manipulated  in  order  to  ascertain  if  there 
was  a  gall-stone  in  the  termination  of  the  common  bile- 
duct,  and  this  may  possibly,  though  if  so,  unconsciously, 
have  dislodged  an  obstruction,  leading  to  relief  of  the 
jaundice.  A  specimen  of  his  urine  was  obtained  in  1904, 
and  although  he  was  reported  to  be  quite  well,  this  was 
found  to  give  crystals  by  the  "A"  reaction,  which  dis- 
solved in  33  per  cent,  sulphuric  acid  solution  in  half  a 
minute,  and  to  contain  sugar  in  fair  quantity. 

This,  along  with  other  cases,  shews  that  it  is  unwise 
not  to  thoroughly  drain  the  bile-ducts  in  all  such  doubtful 
cases,  and  if  cholecystenterostomy  is  not  performed, 
drainage  ought  to  be  continued  until  the  bile  becomes 
free  from  organisms  and  its  normal  route  is  free  from 
obstruction. 

In  certain  cases,  doubtless,  recovery  occurs  without 
operation,  and  we  have  notes  of  one  case  where  a  gentle- 
man of  advanced  age  had  deep  jaundice  associated  with 
glycosuria  and  with  well-marked  pancreatic  reaction  in 
the  urine,  pointing  to  the  case  being  one  of  pancreatic 


Chronic  Pancreatitis  437 

diabetes.  Under  general  treatment,  combined  with 
massage,  he  regained  his  health,  and  is  now  said  to  be 
quite  well.  In  this  case  it  is  quite  possible  that  the  mas- 
sage may  have  dislodged  a  concretion  which  was  blocking 
the  common  bile-duct  and  the  pancreatic  duct,  but  as  no 
search  was  made  in  the  faeces,  this  cannot  be  proved. 
As  the  patient  lives  abroad,  we  have  not  been  able  to 
test  the  urine,  which  will  probably  still  contain  glucose. 

This  case  raises  the  question  whether  operations  ought 
to  be  declined  because  of  the  presence  of  a  small  amount 
of  sugar  in  the  urine.  In  future,  should  the  patient's 
condition  be  fair,  one  would  feel  inclined  to  recommend 
operation  in  order  to  remove  the  obstruction,  and,  by 
drainage,  to  arrest  the  pathological  process  going  on  in 
the  pancreas. 

It  was  only  after  the  complete  and  perfect  recovery 
of  a  case  of  interstitial  pancreatitis  in  1891,  after  the 
performance  of  cholecystotomy  by  one  of  us,  that  the 
indication  for  drainage  of  the  bile-passages  in  inflamma- 
tory swelling  of  the  head  of  the  pancreas  was  made  mani- 
fest.    The  following  is  a  report  of  the  case : 

The  patient,  a  man,  aged  fifty,  was  deeply  jaundiced 
and  supposed  to  be  suffering  from  a  gall-stone  in  the  com- 
mon duct,  but  on  exploration  on  February  17,  1891,  no 
biliary  concretion  could  be  felt,  though  a  swelling  of  the 
head  of  the  pancreas  was  found.  The  patient  recovered 
after  a  simple  cholecystotomy  and  regained  his  health,  but 
we  have  not  been  able  to  trace  his  subsequent  history. 

In  1892  came  the  first  opportunity  of  actually  proving 
the  true  pathological  condition  by  a  microscopic  exami- 
nation of  the  head  of  the  pancreas.  The  following  is  a 
description  of  the  case : 

The  patient  was  a  man,  aged  thirty-two,  w^ho  was  seen 
in  April,  1892.  He  was  extremely  ill  and  emaciated  at 
the  time,  and  sufl:ering  from  deep  jaundice  and  great  pros- 
tration with  dilatation  of  the  gall-bladder.     Operation 


438       The  Pancreas:  Its  Surgery  and  Pathology 

was  undertaken  too  late  and  death  resulted  from  shock 
and  exhaustion  on  the  second  day.  A  necropsy  revealed 
a  cirrhotic  condition  of  the  head  of  the  pancreas  compress- 
ing the  common  bile-duct,  there  being  no  evidence  of 
malignant  disease  (Fig.  137). 


Up  to  this  time  all  the  cases  were  examples  of  chronic 
pancreatitis,   either  independent  of  cholelithiasis,   or  in 
which  no  gall-stones  were  present  at  the  time  of  operation, 
though  one  suspected  that  gall-stones  had  been  the  origi- 
nal   cause     of     the 
trouble  in  both  the 
first    and     second 
cases. 

It  was  not  until 
1895  that  one  of  us 
actually  found  the 
associated  condition 
of  gall-stones  in  the 
common  duct  with 
chronic  interstitial 
pancreatitis ,  and 
after  removing  the 
calculi  from  the 
common  duct, 
short  -  circuited  the 
gall-bladder  into  the 
duodenum,  by  the  operation  of  cholecystenterostomy, 
after  which  the  patient  recovered  and  was  in  excellent 
health  three  years  later.  The  following  is  a  brief  descrip- 
tion of  the  case : 

The  patient,  a  woman  aged  fifty-one,  had  chronic 
jaundice  and  irregular  fever,  associated  with  spasmodic 
pains  and  great  loss  of  flesh.  Operation  was  performed 
on  July  15,  1895,  when  gall-stones  were  removed  from 
the  common  duct  and  a  hard  swelling  of  the  pancreas 
was  felt  which  was  thought  to  be  cancer.     The  gall-bladder 


Fig.  137. — Advanced  chronic  inter- 
stitial pancreatitis  of  the  interlobular  type 
(X  ca  35). 


Chronic  Pancreatitis  ^  439 

was  connected  to  the  duodenum  to  establish  permanent 
drainage.  The  patient  recovered  and  was  in  excellent 
health  three  years  later. 

This  was  followed  shortly  ?jy  other  cases  of  interstitial 
pancreatitis,  some  associated  with  gall-stones,  while 
in  others  there  was  no  evidence  of  cholelithiasis,  but  all 
of  which  were  treated  by  cholecystenterostomy,  which 
has  since  been  repeated  on  numerous  occasions ;  at  times 
the  short-circuiting  operation  alone  being  done,  at  others 
the  operation  being  associated  with  choledochotomy  or 
duodenocholedochotomy. 

The  following  cases  will  serve  as  examples : 

A  man  aged  thirty-four  was  seen  in  1897.  He  had  had 
painful  attacks  resembling  cholelithiasis  since  June  of 
1896,  and  deep  jaundice  since  December.  The  gall- 
bladder was  distended  and  easily  palpated.  The  patient 
was  extremely  ill  and  emaciated.  At  the  operation  on 
February  25,  1897,  the  gall-bladder  was  found  to  be  dilated 
and  surrounded  by  numerous  adhesions,  but  no  gall- 
stones could  be  felt.  Cholecystenterostomy  was  per- 
formed. The  patient  made  a  good  recovery  and  rapidly 
lost  his  jaundice.  His  medical  attendant  was  good 
enough  to  write  on  January  24,  1904,  to  say  that  the 
patient  was  in  good  health  and  had  never  had  a  day's 
illness  since  his  return  home,  the  operation  having  taken 
place  seven  years  previously. 

A  woman  was  seen  who  had  had  gall-stones  removed 
from  the  gall-bladder  three  years  before,  in  Canada. 
She  had  never  been  free  from  jaundice  since  the  opera- 
tion, and  was  subject  to  frequent  vomiting.  She  was 
much  emaciated,  the  stomach  w^as  dilated,  and  there  was 
marked  tenderness  over  the  gall-bladder  region.  At 
the^pperation,  on  October  18,  1897,  ver}^  extensive  adhe- 
sions were  found  and  the  pancreas  was  much  enlarged. 
Cholecystenterostomy  was  performed,  after  which  she 
gradually  regained  her  health.  Her  medical  man  was 
kind  enough  to  send  word  on  January  24,  1904,  that  the 
operation  had  been  a  complete  success  and.  that  the 
patient  was  leading  an  active  life  and  was  well  six  years 
after  operation. 


440       The  Pancreas:  Its  Surgery  and  Pathology 

A  female  patient  was  seen  on  October  20,  1899,  who 
had  been  suffering  for  three  years  from  attacks  resembling 
those  of  gall-stones,  each  attack  being  followed  by  jaun- 
dice. During  the  past  fourteen  weeks  the  seizures  had  been 
more  frequent  and  severe,  and  jaundice  had  never  quite 
cleared  away  before  another  attack  came  on.  She  had 
lost  flesh  and  strength  considerably  and  had  vomited 
from  time  to  time  between  the  attacks.  Her  digestion 
was  much  impaired  and  there  was  a  want  of  appetite. 
She  had  had  no  rigors  and  had  only  slight  fever  at  the 
time  of  each  seizure.  The  urine  contained  abundant 
lithates  and  a  slight  trace  of  albumin,  but  no  sugar.  An 
examination  of  the  abdomen  showed  no  manifest  enlarge- 
ment of  the  liver  or  gall-bladder,  but  some  tenderness 
over  the  gall-bladder  and  at  the  epigastrium,  where  there 
was  an  indefinite  sense  of  fulness.  An  operation  was  per- 
formed on  the  23d,  when,  after  detaching  numerous 
adhesions,  fifteen  gall-stones  were  removed  from  the 
cystic  and  common  ducts,  but,  as  a  large  nodular  mass 
was  occupying  the  head  of  the  pancreas  and  partly  ob- 
structing the  common  duct,  it  was  deemed  advisable  to 
perform  cholecystenterostomy  so  as  to  make  a  perma- 
nent opening  between  the  fundus  of  the  gall-bladder  and 
the  duodenum.  The  tumour  gave  the  impression  that 
it  was  malignant .  Recovery  was ,  however ,  uninterrupted , 
the  button  was  passed  on  the  tenth  day,  the  wound  healed 
by  first  intention,  and  the  patient  immediately  began  to 
put  on  flesh.  She  returned  home  within  the  month  and 
has  since  been  perfectly  well  in  every  respect. 

A  man  aged  twenty-five  was  seen  on  January  11,  1905, 
on  account  of  deep  jaundice  with  serious  deterioration 
of  health,  accompanied  by  loss  of  weight  and  strength. 
He  gave  a  history  that  he  had  been  out  big  game  shooting 
in  Uganda  and  had  had  an  attack  of  fever,  from  which 
he  had  made  a  good  recovery,  returning  home  in  Sep- 
tember, 1904,  in  fairly  good  health.  In  October  he  had 
what  he  took  to  be  a  return  of  the  fever,  the  attack  being 
ushered  in  by  a  rigor,  and  followed,  within  a  few  days,  by 
jaundice,  which  gradually  deepened,  but  he  had  abso- 
lutely no  pain  in  the  abdomen  or  elsewhere.  He  lost  his 
appetite  forthwith,  and  speedily  began  to  lose  flesh,  so 
that  when  he  was  seen  his  weight  was  less  by  a  stone  than 


Chronic  Pancreatitis 


441 


on  his  return  home.  There  had  been  neither  sickness 
nor  vomiting  since  November,  and  he  had  had  no  more 
rigors.  His  pulse  had  been  very  slow  (from  40  to  50)  and 
the  temperature  subnormal.  These  symptoms  continued 
up  to  the  time  he  was  seen,  when  he  was  found  to  be 
suffering  from  deep,  almost  black,  jaundice,  and  from 
anaemia.  The  liver  reached  well  below  the  costal  margin, 
almost  to  the  umbilicus,  but  the  spleen  could  not  be  felt. 
A  little  tenderness  was  elicited  an  inch  above  the  umbili- 
cus and  half  an  inch  to  the  right  of  the  middle  line,  where 
it  was  thought  a 
slight  fulness  could 
be  felt,  but  this  was 
indefinite.  No  dila- 
tation of  the  stom- 
ach could  be  made 
out,  and  beyond  the 
jaundice,  with  the 
pale  motions  and 
dark  urine,  no  other 
physical  signs  could 
be  elicited.  The 
motions  were  bulky, 
but  not  frequent ,  and 
there  was  no  tend- 
ency to  diarrhoea. 
The  tongue  was 
somewhat  coated. 
Chronic  pancreatitis 
was  suspected  and 
the  urine  and  faeces 
were  examined,  the 
following  being  the 

report:  Urine — Reaction,  acid.  Specific  gravity,  1.014. 
Albumin,  nil;  some  nucleo-proteid.  Dextrose,  nil.  Pen- 
tose, nil.  Maltose,  nil.  Glycuronic  acid  reaction,  nega- 
tive. Indican,  marked  reaction.  Ferric  chloride  reac- 
tion, negative.  Bile-pigment,  much.  Microscopically, 
a  few  bile-stained  epithelial  cells.  "  Pancreatic  reaction"  : 
"A,"  many  fine  crystals  soluble  in  33  per  cent,  sulphuric 
acid  in  one-half  to  three-quarters  of  a  minute  (Fig.  138) ; 
"B,"  some  fine  crystals  soluble  in  33  per  cent,  sulphuric 


Fig.  138. — Crystals  from  the  urine  ob- 
tained by  the  "A-reaction"  in  a  case  of 
chronic  pancreatitis  (X  190)  described  in 
the  text. 


442       The  Pancreas:  Its  Surgery  and  Pathology 

acid  in  one  minute.  Fseces^ — Reaction,  alkaline.  Sterco- 
bilin,  traces.  Microscopically,  crowds  of  fat  globules,  many 
fatty  acid  crystals,  much  vegetable  tissue,  some  partly 
digested  muscle  fibre,  epithelial  cells,  and  granular  debris. 
Total,  fat,  56.8  per  cent.;  neutral  fat,  29.5  per  cent.; 
fatty  acids,  27.3  per  cent. 

These  results  indicated  a  pancreatic  lesion  of  an  inflam- 
matory nature.  The  character  of  the  crystals  obtained 
from  the  urine  and  the  relations  of  the  "A"  and  "B" 
reactions  suggested  that,  while  the  condition  was  probably 
of  some  standing,  there  was  at  the  time  some  active  inflam- 
mation of  the  gland.  The  large  amount  of  bile-pigment  in 
the  urine,  and  its  almost  complete  absence  from  the  f^ces, 
together  with  the  high  percentage  of  fat  and  the  presence 
of  muscle  fibre  in  the  latter,  pointed  to  an  obstruction  of 
the  common  duct  as  the  probable  cause  of  the  condition. 
The  considerable  reaction  for  indican  given  by  the  urine 
suggested  that  there  was  some  catarrh  of  the  upper  part 
of  the  intestine. 

As  medical  treatment  with  rest  in  bed  and  care  in  diet 
had  been  thoroughly  tried  without  any  benefit,  an  opera- 
tion was  advised..  This  was  performed  at  a  nursing  home 
on  January  16,  1905.  On  opening  the  abdomen  by  a 
vertical  incision  through  the  centre  of  the  right  rectus 
a  little  ascitic  fluid,  deeply  bile-stained,  escaped.  The 
liver  was  found  to  be  enlarged  nearly  to  the  umbilicus. 
It  was  dark  and  mottled,  and  showed  evidences  of  cirrho- 
sis, apparently  due  to  biliary  stagnation.  The  gall- 
bladder was  thickened,  but  not  greatly  distended,  though 
it  had  evidently  been  inflamed,  as  adhesions  were  found 
between  it  and  the  cystic  and  common  ducts  and  the 
neighbouring  viscera,  stomach,  duodenum,  and  colon. 
The  foramen  of  WinsloAV  was  obliterated  by  adhesions. 
The  head  of  the  pancreas  was  much  enlarged  and  widened 
in  area,  so  that  it  extended  some  distance  up  by  the  side 
of  the  common  duct,  which  it  enveloped.  A  hard  nodule 
could  be  felt  in  the  head  of  the  pancreas,  which  hardness 
could  be  traced  into  the  wall  of  the  duodenum,  and  which 
faded  off  into  the  body  of  the  pancreas,  the  body  and  tail 
of  the  organ  being  apparently  of  almost  normal  consis- 
tency. Adjoining  the  portion  of  the  pancreas,  which 
was  stony  hard,  could  be  seen  a  number  of  lobules  of  the 


Chronic  Pancreatitis 


443 


pancreas,  which  were  firmer  than  normal  and  very  defi- 
nitely outlined,  a  condition  seen  in  a  number  of  cases  of 
chronic  interstitial  pancreatitis  previously  operated  on. 
The  localised  hardness  raised  the  question  as  to  whether 
there  might  be  a  growth  of  the  papilla  extending  into  the 
duodenum,  or  whether  there  might  possibly  be  a  pancre- 
atic calculus  impacted  in  the  duct.  It  was  therefore  felt 
desirable  to  thoroughly  explore  the  pancreas,  and  to 
this  end  the  visceral  peritoneum  was  incised  over  the 
duodenum  and  stripped  from  the  pancreas.  An  incision 
was  made  into  the  indurated  area  and  a  portion  of  the 
hardened  mass  was  removed.     Although  very  hard,   it 


Fig.  139.^ — Section  of  a  nodule  of  pancreatic  tissue  removed  at 
operation,  showing  chronic  interstitial  pancreatitis:  a.  Low  power 
(X  ca  37);   b,  high  power  (X  ca  190). 

did  not  cut  like  cartilage  and  had  not  the  appearance  of 
a  malignant  growth.  Subsequent  microscopical  exami- 
nation showed  well-marked  interstitial  pancreatitis  (Fig. 
139).  No  calculus  could  be  found.  The  incision  in  the 
pancreas  was  then  closed  by  several  catgut  sutures,  and 
the  peritoneum  replaced.  The  duodenum  was  then 
opened  in  the  centre  of  the  descending  portion,  w^hen  a 
hard  lobule  was  felt  on  the  inner  side  of  the  papilla,  and 
this  proved  to  be  continuous  with  the  stony  hard  lump 
in  the  head  of  the  pancreas.  It  was  suspected  that  this 
was  an  accessory  pancreas  in  the  wall  of  the  duodenum. 
It  was  not  ulcerated,  and  did  not  give  the  impression 
of  being  malignant.     The  common  bile-duct  was  clearly 


441       The  Pancreas:  Its  Surgery  and  Pathology 

compressed  by  the  hardened  head  of  the  pancreas,  and 
in  order  to  estabHsh  drainage  of  the  infected  bile  the  only 
desirable  course  seemed  to  be  that  of  performing  a  chole- 
cystenterostomy.  The  opening  made  for  exploration 
into  the  duodenum  was  therefore  united  to  one  made  in 
the  fundus  of  the  gall-bladder  by  means  of  a  Murphy 
button,  and  the  abdomen  was  closed  without  drainage. 
The  operation  was  unaccompanied  by  haemorrhage,  as 
chloride  of  calcium  had  been  given  in  20-grain  doses  thrice 
daily  for  three  days  before  operation,  and  the  drug  was 
continued  subsequently  to  operation  in  30-grain  doses  in 
the  nutrient  injections  for  a  few  days.  The  after-progress 
was  very  satisfactory.  The  wound  healed  entirely  by 
first  intention,  and  the  jaundice  began  to  diminish  visibly 
within  two  days  of  operation.  His  bowels  were  moved 
on  the  fourth  day  after  a  dose  of  calomel,  the  motions 
showing  the  presence  of  bile.  His  appetite  rapidly 
returned,  and,  after  the  button  had  passed  on  the  tenth 
day,  he  was  allowed  to  take  food  freely,  his  appetite 
being  very  keen.  At  first  the  motions  were  bulky,  fre- 
quent, and  offensive,  evidently  due  to  the  passage  of 
undigested  milk.  Pankreon  tablets  were  therefore  given 
after  each  meal,  with  the  result  that  the  food  was  better 
digested,  and  the  motions  were  diminished  in  number. 

An  examination  of  the  blood  was  made  on  January  26th 
with  the  following  result:  Red  corpuscles,  3,472,000  per 
cubic  millimetre.  Haemoglobin,  58  per  cent.  Haemoglo- 
bin index,  0.58.  White  corpuscles,  9,965  per  cubic  milli- 
metre. Proportion  of  red  to  white  corpuscles,  348  to  i. 
Differential  leucocyte  count:  Polymorphonuclear  white 
cells,  71  per  cent.;  small  lymphocytes,  22  per  cent.; 
large  lymphocytes,  4  per  cent. ;  eosinophile  leucocytes,  3 
per  .cent. ;  mast  cells,  i  per  cent. 

At  the  end  of  the  third  week  the  patient  was  able  to 
sit  up,  and  when  he  was  weighed  at  the  month-end  he  had 
gained  a  stone  in  weight,  and  expressed  himself  as  feeling 
well.  His  blood,  urine,  and  fasces  were  examined  again 
on  February  20th,  with  the  following  result: 

Blood. — Red  corpuscles,  4,634,000  per  cubic  millimetre. 
Haemoglobin,  92  per  cent.  Haemoglobin  index,  i.o. 
White  corpuscles,  5,855  per  cubic  millimetre.  Propor- 
tion of  red  to  white  corpuscles,   791  to  i.     Differential 


Chronic  Pancreatitis  445 

leucocyte  count:  Polymorphonuclear  white  cells,  70  per 
cent.;  small  lymphocytes,  22  per  cent.;  large  lympho- 
cytes, 3  percent. ;  eosinophile leucocytes,  4  per  cent. ;  mast 
cells,  0.5  per  cent. 

Urine. — Reaction,  acid.  Specific  gravity,  1.022.  Al- 
bumin, nil.  Dextrose,  nil.  Pentose,  nil.  Maltose,  nil. 
Glycuronic  acid  reaction,  negative.  Indican,  trace.  Fer- 
ric chloride  reaction,  negative.  Bile-pigment,  faint  traces. 
Microscopically,  urates.  Pancreatic  reaction :  "A,"  a  few 
fine  crystals  soluble  in  33  per  cent,  sulphuric  acid  in 
three-quarters  to  one  minute;  "B,"  a  few  fine  crystals 
soluble  in  33  per  cent,  sulphuric  acid  in  one  minute. 

This  specimen  of  urine  shows  a  marked  improvement 
on  that  examined  on  January  12th.  The  pancreatic 
reaction  was  only  slight,  and  the  amount  obtained  by  the 
"A"  and  "B"  methods  equal,  indicating  probably  the 
fibrotic  changes  following  the  pancreatitis  previously 
found.  There  was  still  a  faint  trace  of  bile-pigment  in  the 
urine,  but  it  was  exceedingly  slight  compared  with  the 
large  amount  present  on  the  last  examination.  The 
indican  reaction  was  very  much  diminished,  and  was  not 
much  more  than  is  at  times  found  in  health. 

FtFC^.s-.— Reaction,  alkaline.  Stercobilin,  a  considera- 
ble amount.  Microscopically,  vegetable  tissue,  granular 
debris,  no  fatty  globules  or  fatty  acid  crystals,  no  muscle 
fibre.  Total  fat,  15  per  cent.;  fatty  acids,  11  per  cent.; 
neutral  fat,  4  per  cent. 

On  February  20th,  when  the  patient  left  the  nursing 
home,  his  weight  had  increased  to  10  stones  9  pounds, 
it  having  been  9  stones  on  admission.  It  will  be  seen 
that  whereas  before  operation  the  total  fat  in  the  fasces 
was  56.8  per  cent.,  on  February  20th  it  had  diminished 
to  15  per  cent.,  the  fatty  acids,  which  were  27.3  per  cent. 
January  12th,  had  diminished  to  11  per  cent,  on  Feb- 
ruary 20th;  and  the  neutral  fat,  which  was  29.5  per  cent, 
on  January  12th,  had  diminished  to  4  per  cent,  on  Feb- 
ruary 20th.  The  blood  had  also  very  materially  improved, 
as  will  be  seen  on  comparing  the  reports,  for  as  on  Jan- 
uary 26th  the  red  corpuscles  were  3,427,000  per  cubic 
millimetre,  on  February  20th  they  were  4,634,000  per 
cubic  millimetre;  the  h^emiOglobin,  which  on  January 
26th  was  58  per  cent.,  on  February  20th  was  92  per  cent. ; 


446       The  Pancreas:  Its  Surgery  and  Pathology 

the  hsemoglobin  index  on  January  26th  was  0.85,  on 
February  20-th  it  was  i.o ;  the  white  corpuscles,  which  on 
January  26th  numbered  9965  per  cubic  millimetre,  on 
February  26th  had  diminished  to  5855  ;  and  the  propor- 
tion of  red  to  white  corpuscles,  which  on  January  26th 
was  as  348  to  i,  on  February  20th  wa's  in  the  proportion 
of  791  to  I. 

A  simple  drainage  of  the  gall-bladder  by  cholecystotomy 
is  frequently  unsatisfactory,  and  cannot  be  relied  on  in 
well-marked  cases  of  obstruction,  as  the  drainage  of  the 
bile-passages  is  not  sufficiently  long  continued.  This 
applies  especially  to  the  cases  in  which  the  interstitial 
pancreatitis  has  persisted  for  some  length  of  time,  in 
which  cases,  although  a  cholecystotomy  may  lead  to  a 
disappearance  of  the  jaundice  and  the  digestive  symp- 
toms may  be  alleviated,  the  metabolic  signs  found  in  the 
urine  many  months  or  even  years  subsequently  show 
that  recovery  has  only  been  partial. 

The  following  are  examples: 

Mr:  D ,  aged  forty-five,  had  had  painful  epigastric 

attacks  for  twelve  months,  with  vomiting,  but  no  jaun- 
dice. There  had  been  deep  jaundice  since  January  last, 
with  ague-like  attacks,  and  the  patient  had  lost  2^  stones 
in  weight.  Cholecystotomy  was  performed  on  March 
29,  1898.  Thickened  duct  felt,  together  with  a  swelling 
of  the  pancreas,  thought  to  be  cancer  of  the  head  of  the 
pancreas  and  the  common  bile-duct.  Drainage  of  the 
gall-bladder  for  ten  days.  The  patient  made  a  complete 
recovery,  and  in  August  was  apparently  quite  well, 
having  gained  a  stone  in  weight.  He  was  in  good  health 
in  1 90 1.  Though  apparently  well  in  January,  1904,  an 
examination  of  the  urine  gave  the  pancreatic  reaction 
and  showed  that  the  original  damage  to  the  pancreas 
had  not  been  completely  repaired. 

Mrs.  D ,  aged  forty-six,  had  had  spasms  for  years. 

Acute  seizure  in  July  and  three  times  since.  Since  July, 
pain  and  sickness  every  two  weeks.  No  tumour  felt  at 
any  time ;  jaundiced  occasionally  after  an  attack  of  pain ; 


Chronic  Pancreatitis  447 

lost  one  stone  in  weight.  She  had  never  vomited  blood 
and  never  had  melaina.  There  was  tenderness  over  the 
gall-bladder,  but  no  tumour.  Slight  enlargement  of  the 
head  of  the  pancreas.  Cholecystotomy  was  perfonned 
on  December  11,  1899.  Empyema  of  the  gall-bladder. 
Many  stones  removed  from  the  gall-bladder  and  cystic 
duct.  Adhesions  broken  down.  Xodular  condition  of 
the  head  of  the  pancreas  found.  The  patient  made  a 
good  recovery  and  was  well  in  1904,  though  an  examina- 
tion of  the  urine  showed  the  A  and  B  jjancreatic  reaction 
and  proved  that  the  metabolic  functions  of  the  pancreas 
were  still  not  normal. 

In  some  cases  where  operation  has  been  delayed,  or 
drainage  of  the  bile-ducts  not  performed  or  not  long  enough 
continued,  the  original  interstitial  pancreatitis  may 
advance  so  that  the  islands  of  Langerhans  become  in- 
volved, and  glycosuria  ensues,  as  in  the  two  following 
cases : 

Mrs.    C ,    aged   fifty-one,   who  was   suffering  from 

persistent  jaundice,  with  periodical  pains,  and  ague-like 
seizures  that  had  extended  over  a  long  period,  was  oper- 
ated on  in  July,  1895,  when  several  gall-stones  were 
removed  and  others  crushed  in  the  common  duct.  A 
tumour  of  the  pancreas  was  felt,  which  it  was  thought 
at  the  time  might  be  malignant.  The  gall-bladder  was 
therefore  drained  into  the  duodenum  by  a  cholecysten- 
terostomy.  The  patient  completely  recovered,  and  has 
remained  well  since  the  operation,  over  nine  years  ago, 
but  an  examination  of  the  urine  showed  there  to  be  an 
abundance  of  dextrose,  but  no  acetone  or  diacetic  acid. 
Pancreatic  crystals  were  obtained  by  the  '"A"  reaction, 
which  dissolved  in  three-quarters  to  one  minute,  but  none 
could  be  isolated  by  the  "B"  method.  This  showed 
that  although  the  patient  has  been  relieved  by  the  opera- 
tion, and  had  apparently  enjoyed  good  health,  yet  that 
she  was  living  with  a  damaged  pancreas  and  consequent 
glycosuria. 

A  man,  aged  forty-five,  was  seen  on  the  25th  of  October, 
1898.     The  patient  was  very  deeply  jaundiced,  and  said 


448       The  Pancreas:  Its  Surgery  and  Pathology 

that  he  had  lost  a  stone  in.  weight  since  the  onset  of  his 
illness,  five  weeks  before.  He  gave  the  history  of  having 
had  attacks  of  pain,  referred  to  the  region  of  the  gall- 
bladder, nine  years  previously,  but  they  were  unaccom- 
panied by  jaundice  and  passed  off  after  prolonged  treat- 
ment. From  that  time  onwards  he  had  been  free  from 
attacks  of  pain  up  to  the  onset  of  the  present  illness,  five 
weeks  before,  when  he  was  suddenly  seized  with  severe 
pain  at  the  pit  of  the  stomach  and  became  jaundiced. 
The  pain  had  recurred  daily  and  had  been  so  severe  as  to 
necessitate  his  taking  morphia.  His  medical  attendant 
noticed  a  swelling  in  the  region  of  the  gall-bladder  a  fort- 
night after  the  onset  of  his  illness,  and  there  was  all  along 
well-marked  tenderness  at  the  epigastrium,  with  gradually 
increasing  enlargement  of  the  liver.  The  patient's  gen- 
eral health  rapidly  failed,  and  the  loss  of  flesh  was  well 
marked.  When  seen  he  looked  pinched  and  ill,  he  was 
very  deeply  jaundiced,  and  the  urine  was  loaded  with 
lithates,  but  contained  neither  albumin  nor  sugar. 
There  were  well-marked  tenderness  at  the  epigastrium 
and  a  smooth  tumour,  which  was  not  very  tender,  in  the 
gall-bladder  region;  the  liver  was  enlarged  and  the 
edge  was  smooth  and  could  easily  be  felt  an  inch  below 
the  costal  margin.  A  diagnosis  of  gall-stones  in  the  com- 
mon duct  was  made  and  the  patient  was  admitted  into 
hospital.  The  operation  was  performed  on  September 
27,  1898.  On  opening  the  abdomen  numerous  adhesions 
between  the  gall-bladder  and  liver,  and  the  pylorus,  colon, 
omentum,  and  duodenum  were  found.  The  gall-bladder 
was  slightly  distended,  but  no  gall-stones  were  felt  either 
in  it  or  in  the  cystic  or  common  duct.  There  was,  how- 
ever, a  hard  nodular  swelling  of  the  head  of  the  pancreas, 
which,  at  the  time,  was  thought  to  be  malignant.  In 
order  to  give  relief,  the  adhesions  were  detached  and  the 
gall-bladder  was  drained  by  cholecystotomy.  On  Octo- 
ber 28th  a  letter  was  sent  to  his  medical  man,  telling  him 
that  we  feared  the  disease  of  the  pancreas  might  be  malig- 
nant, but  that  there  was  a  possibility  of  its  being  a  chronic 
pancreatitis.  On  November  5th  another  letter  was  writ- 
ten by  one  of  us,  to  this  effect:  "  I  am  pleased  to  be  able 
to  tell  you  that  your  patient  has  improved  very  much 
and  the  jaundice  has  nearly  disappeared.     I  hope,  there- 


Chronic  Pancreatitis  449 

fore,  that  the  tumour  of  the  head  of  the  pancreas  may 
have  been  inflammatory,  and  not  malignant.  At  the 
time  of  operation  it  occurred  to  me  that  it  was  not  quite 
hard  enough  for  a  malignant  tumour,  but  under  the  cir- 
cumstances I  felt  it  my  duty  to  give  you  my  suspicions." 
From  that  time  onwards  recovery, was  uninterrupted, 
and  the  patient  left  the  hospital  with  the  wound  closed, 
within  the  month.  In  December,  1899,  the  patient  called 
to  report  himself.  He  looked  perfectly  healthy  and  had 
gained  over  a  stone  in  weight  since  his  return  home. 
He  had  neither  pain  nor  tenderness  and  he  said  he  felt  as 
well  as  if  he  had  never  ailed  anything.  The  scar  was  firm, 
the  liver  was  normal,  and  there  was  not  the  slightest  ten- 
derness in  the  epigastrium  or  in  the  gall-bladder  region. 
Five  years  later  the  patient  was  apparently  well  so  far  as 
the  local  symptoms  were  concerned,  but  an  examination 
of  the  urine  showed  the  presence  of  glucose  and  the  pan- 
creatic reaction  was  present,  thus  pointing  to  the  persis- 
tence of  chronic  interstitial  pancreatitis,  which  had 
evidently  extended  and  invaded  the  islands  of  Langerhans. 
The  urine  contained  no  bile  and  no  albumin,  but  an  abun- 
dance of  oxalates. 

Had  the  gall-bladder  been  longer  drained  in  this  case 
or  cholecystenterostomy  performed,  it  seems  highly  prob- 
able, arguing  from  the  results  of  operation  in  other  cases, 
that  the  sequelae  above  mentioned  might  have  been  pre- 
vented. 

Occasionally,  however,  the  simple  operation  of  chole- 
cystotomy  may  be  sufficient  to  bring  about  a  cure,  as 
in  the  following  cases : 

The  patient,  a  man  aged  forty-five,  was  seen  on  March 
19,  1898,  the  history  being  that  he  had  been  well  up  to 
twelve  months  before,  when  he  began  to  have  painful 
attacks  at  the  pit  of  the  stomach,  ending  in  vomiting,  but 
not  followed  by  jaundice  until  an  attack  on  January  i, 
1898,  since  which  time  he  had  been  deeply  and  continu- 
ously jaundiced.  He  had  also  from  that  time  onwards 
had  ague-like  attacks,  and  two  days  before  he  was  seen 
he  had  had  within  twenty-four  hours  three  of  these 
29 


450      The  Pancreas:  Its  Surgery  and  Pathology 

seizures,  each  accompanied  by  pain.  Within  a  twelve- 
month he  had  lost  2  stones  8  pounds  in  weight.  On 
examining  him  there  was  some  swelling  in  the  gall-bladder 
region  but  no  tenderness.  The  liver  was  a  little  enlarged 
but  the  margins  felt  smooth.  There  was  decided  tender- 
ness in  the  middle  line  just  above  the  umbilicus,  and  on 
deep  pressure  the  pain  was  considerable  and  an  indefinite 
fulness  could  be  felt.  The  diagnosis  of  gall-stones  in  the 
common  duct  was  made,  and  an  operation  was  advised. 
The  patient  was  operated  on  on  March  30th,  when  the 
gall-bladder  was  found  to  be  slightly  distended  and  sur- 
rounded by  adhesions  to  the  pylorus,  duodenum,  colon, 
and  omentum.  No  gall-stones  could  be  discovered,  but 
there  was  a  well-marked  swelling  of  the  head  and  the 
first  two  inches  of  the  pancreas,  which,  though  nodular 
and  irregular,  was  not  very  hard.  This  extended  further 
to  the  right  than  normal,  so  as  to  cover  in  the  lower  end 
of  the  common  bile-duct.  Cholecystotomy  was  per- 
formed. Within  twenty-four  hours  of  the  operation 
nearly  four  pints  of  very  offensive  bile  were  discharged 
through  the  tube.  A  specimen  was  examined  by  the 
Clinical  Research  Association  and  their  report  was  as 
follows:  "The  bile  contains  both  staphylococci  and 
streptococci,  but  no  bacillus  coli  communis  could  be  found 
either  under  the  microscope  or  in  the  culture."  Fearing 
that  the  disease  might  be  malignant,  and  the  patient  being 
so  extremely  weak  and  ill,  a  poor  prognosis  was  given, 
but  in  a  few  days  the  following  report  was  given:  "The 
patient  is  progressing  satisfactorily,  though  he  is  still  pro- 
foundly weak.  Bile  has  appeared  in  the  motions  so  that 
the  obstruction  is  evidently  overcome.  The  bowels 
have  been  moved  naturally  and  the  patient  is  less  deeply 
jaundiced  and  looking  better  generally."  On  April  5th 
he  was  taking  his  food  well  and  bile  was  passing  freely 
in  the  motions.  He  had  had  no  recurrence  of  the  shiver- 
ing attacks.  Drainage  was  continued  for  fourteen  days 
and  the  patient  returned  home  on  the  20th.  The  urine 
was  then  free  from  bile  and  the  motions  were  assuming 
a  natural  colour;  he  was  taking  food  well,  gaining  flesh, 
and  looking  better  generally.  A  guarded  prognosis  was 
still  given,  however,  as  it  was  thought  that  the  tumour 
would   prove   to   be   inflammatory   and   not   malignant. 


Chronic  Pancreatitis  451 

From  that  time  onwards  his  progress  to  recovery  was 
extremely  rapid,  and  he  was  said  to  be  perfectly  well  in 
every  respect  a  few  months  later,  and  had  fully  regained 
his  lost  weight.  Two  years  later  he  was  still  in  perfectly 
good  health. 

A  woman,  aged  thirty-five,  was  seen  on  September  11, 
1899,  with  the  history  of  having  been  subject  to  attacks 
of  spasms  in  the  upper  abdominal  region  for  twelve 
years,  the  intervals  between  the  seizures  having  varied 
from  a  few  days  to  several  months,  but  of  late  they  had 
become  much  more  frequent,  and  during  the  week  before 
she  was  seen  she  had  had  four  attacks,  all  severe  ones. 
The  seizures  began  with  pain  in  the  epigastrium  accom- 
panied by  cold  sweats  and  faintness;  the  pain  passed 
through  the  midscapular  and  to  the  right  subscapular 
region,  and  lasted  from  two  to  six  hours,  having  to  be 
relieved  at  times  by  morphia.  Jaundice  followed  the 
seizures,  and  if  the  attacks  recurred  frequently  it  was  in- 
tensified with  each,  but  if  there  was  a  long  interval  only 
an  icteric  tinge  remained.  Palpation  revealed  a  point 
of  tenderness  in  the  mid-line,  one-and-a-half  inches  above 
the  umbilicus,  where  there  was  a  sense  of  resistance  with 
an  abnormal  fulness,  but  there  was  no  tenderness  over 
the  gall-bladder,  nor  could  any  swelling  of  the  gall-blad- 
der or  liver  be  discovered.  On  September  21st  a  vertical 
incision  through  the  right  rectus  exposed  adherent  viscera, 
and,  on  the  separation  of  the  adhesions,  a  thickened 
gall-bladder  was  exposed,  but  there  were  no  gall-stones 
in  it  or  in  the  ducts.  The  lower  part  of  the  common 
duct  was  surrounded  and  overlaid  by  a  well-marked 
swelling  of  the  pancreas,  which  was  harder  than'  usual, 
but  not  sufficiently  hard  to  be  mistaken  for  cancer,  though 
it  was  somewhat  nodular.  Cholecystotomy  was  performed 
and  drainage  was  carried  out  for  a  fortnight.  Recovery 
was  uninterrupted  and  the  patient  returned  home  within 
the  month,  and  she  has  remained  well  since. 

If  the  gall-stone  causing  obstruction  be  removed  by 
operation  from  the  common  duct,  and  drainage  of  the 
infected  bile-ducts  be  effected  before  the  catarrhal  has 
passed  into  the  interstitial  form  of  pancreatitis,  a  com- 


452       The  Pancreas:  Its  Surgery  and  Pathology 

plete  cure  may  be  expected  even  after  simple  drainage  of 
the  bile-ducts,  as  in  the  following  cases: 

A  lady,  aged  thirty-four,  had  had  symptoms  of  gall- 
stones for  four  years,  and  had  been  under  treatment  for 
ulcer  of  the  stomach,  but  there  had  been  no  hsematemesis. 
Four  months  previously  jaundice  had  come  on  after  an 
attack  of  pain,  since  which  time  the  attacks  had  been 
frequent  and  were  always  followed  by  an  increase  of  the 
jaundice,  and  by  rigors  and  fever.  On  one  occasion  the 
gall-bladder  was  distended ;  when  seen  there  was  a  slight 
tinge  of  jaundice.  She  had  lost  3  stones  in  weight.  There 
was  an  absence  of  enlargement  of  the  liver  or  gall-bladder, 
but  marked  tenderness  over  the  gall-bladder  was  elicited . 
Pancreatic  crystals  were  found  in  the  urine  and  digestive 
symptoms  were  present.  At  the  operation,  on  April  23, 
1903,  one  large  calculus  was  removed  from  the  cystic 
duct,  and  some  smaller  ones  from  the  common  duct,  by 
separate  incisions  in  the  two  ducts.  The  common  duct 
was  sutured  and  the  cystic  duct  drained.  The  pancreas 
was  slightly  swollen.  The  patient  made  a  good  recovery 
and  remains  well. 

The  explanation  of  the  pancreatitis  in  these  two  cases 
was  manifestly  the  obstruction  of  the  pancreatic  duct 
and  infection  of  the  secretion ;  but  the  complete  recovery 
after  operation  showed  that  the  inflammation  was  prob- 
ably only  catarrhal  and  not  advanced  interstitial  trouble. 

If  the  gall-stone  obstructs  the  common  duct  for  long, 
what  was  at  first  a  simple  catarrhal  pancreatitis  may 
assume  a  truly  interstitial  form,  and  unless  drainage  of 
the  bile-ducts  is  continued  for  some  time  or  permanent 
drainage  in  the  shape  of  cholecystenterostomy  is  estab- 
lished, relapse  will  speedily  occur.  The  following  case 
is  an  example : 

Mrs.  W — — ,  aged  fifty-seven,  had  had  two  operations 
previously  in  Scotland.  On  the  occasion  of  the  first 
operation,  in  September,  1902,  a  number  of  gall-stones 
were  removed  from  the  gall-bladder,  which  was  drained 


Chronic  Pancreatitis  453 

for  a  few  days,  but  after  the  wound  had  healed  the  attacks 
had  been  repeated  as  before.  A  second  operation  was 
undertaken  by  the  same  surgeon  without  finding  any- 
thing definite.  After  the  wound  had  healed,  and  the 
temporary  drainage  had  ceased,  the  attacks  again  re- 
turned, and  the  subsequent  history  up  to  the  time  of  our 
seeing  her  was  that  she  had  almost  daily  attacks  of  pain, 
followed  by  slight  jaundice,  and  on  five  or  six  occasions, 
usually  at  intervals  of  a  month,  she  had  had  violent  seiz- 
ures necessitating  the  use  of  morphia.  About  five  weeks 
before  being  seen  by  us  the  pain  was  so  violent  as  to  cause 
her  to  faint,  and  just  before  coming  to  London  another 
violent  seizure,  accompanied  by  collapse,  occurred.  A 
rigor  with  high  temperature,  104°  or  105°,  had  followed 
each  attack,  the  temperature  between  the  seizures  ris- 
ing nightly  to  101°  or  io2°F.  She  was  rapidly  losing 
flesh  and  strength.  An  examination  of  the  urine  showed 
no  albumin  or  sugar,  but  well-marked  pancreatic  crystals 
by  the  A  reaction,  which  dissolved  in  from  one  to  one-and- 
a-half  minutes,  and  a  smaller  number  of  similar  crystals 
by  the  B  method,  rendering,  along  with  other  signs,  the 
diagnosis  of  chronic  pancreatitis  certain.  At  the  opera- 
tion on  November  20,  1903,  the  adhesions  w^ere  found  to  be 
most  extensive.  There  was  well-marked  enlargement 
and  hardness  of  the  pancreas  along  its  whole  length, 
but  it  was  not  nodular.  The  common  duct  was  carefully 
examined,  but  found  to  be  free  from  concretions,  and  on 
opening  the  gall-bladder  a  probe  was  passed  through  it 
and  the  cystic  and  common  ducts  into  the  duodenum. 
While  the  probe  was  in  position,  the  pancreas  was  manip- 
ulated and  found  to  compress  the  duct,  thus  accounting 
for  the  obstruction.  Cholecystenterostomy  was  there- 
fore performed,  the  union  being  effected  by  means  of  a 
decalcified  bone  bobbin.  At  the  time  of  operation  the 
gall-bladder  was  separated  from  its  fissure  in  the  liver 
in  order  to  make  it  reach  the  bowel  without  tension. 
For  a  few  days  after  operation  bile  was  discharged  from 
the  torn  liver  surface  in  free  quantities,  but  there  was  no 
leakage  from  the  newly  joined  viscera.  As  the  bile 
obtained  a  free  passage  into  the  bowel,  it  gradually  ceased 
being  discharged  from  the  liver,  and  the  tube  was  able 
to  be  left  out  at  the  end  of  ten  days.     The  wound  healed 


454       The  Pancreas:  Its  Surgery  and  Pathology 

by  first  intention  and  the  patient  was  up  at  the  end  of 
three  weeks.  She  was  then  able  to  take  and  digest  her 
food,  and  has  since  been  quite  free  from  her  old  attacks. 

After  cholecystotomy,  the  patient  may  become  impa- 
tient of  the  continued  drainage  and  demand  too  speedy 
relief.     This  was  well  shown  in  the  following  case : 

A  military  officer,  aged  sixty,  was  seen  on  the  8th  of 
July,  1904,  He  was  in  good  health  up  to  May  2d  of  that 
year,  when  painless  jaundice  developed.  He  had  a  feel- 
ing of  discomfort  after  food,  the  jaundice  deepened,  and 
he  rapidly  lost  flesh .  When  seen  he  was  deeply  j  aundiced , 
the  liver  was  enlarged,  nearly  to  the  umbilicus,  and  the 
gall-bladder  was  distended.  He  said  he  had  no  pain  and 
there  was  no  evidence  of  ascites  or  oedema  of  the  legs. 
As  he  did  not  improve  at  all  under  general  treatment, 
and  an  examination  of  the  urine  showed  many  oxalate 
crystals,  and  a  well-marked  pancreatic  reaction,  and  the 
faeces  were  acid  in  reaction,  and  contained  58.7  per  cent, 
of  the  dry  weight  as  fat,  of  which  31.4  per  cent,  was  neu- 
tral fat,  and  27  per  cent,  fatty  acid,  a  diagnosis  of  intersti- 
tial pancreatitis  was  made,  and  operation  was  performed 
on  July  20,  1904,  when  the  pancreas  was  found  to  be  much 
enlarged  and  compressing  the  common  bile-duct.  There 
was  no  positive  evidence  of  malignant  disease,  as  although 
the  glands  were  enlarged,  they  were  discrete  and  not 
nodular.  As  there  was  a  decided  haemorrhagic  tendency, 
and  the  patient  was  too  ill  to  bear  a  prolonged  operation, 
the  enlarged  gall-bladder  was  simply  drained  by  cholecys- 
totomy. The  patient  made  a  good  recovery  and  improved 
considerably  in  his  general  health,  and  the  jaundice  en- 
tirely disappeared.  In  consequence  of  our  temporary 
absence  on  a  holiday  the  patient  got  uneasy  about  the 
persistent  discharge  of  bile  and  was  advised  to  consult 
another  surgeon,  although  he  had  been  counselled  to  bear 
with  the  cholecystotomy  for  at  least  two  months  before 
having  anything  further  done.  Despite  this  advice,  and 
without  our  knowledge,  the  gall-bladder  was  short-cir- 
cuited into  the  colon.  After  the  operation  he  was  very 
much  distressed  by  diarrhoea,  and  after  a  time  he  began 
to  suffer  from  symptoms  of  septicaemia  with  rigors,  which 


Chronic  Pancreatitis  455 

ended  in  death  from  pycemia.  At  the  autopsy  the  infec- 
tion of  the  bile-passages  was  found  to  have  occurred 
through  the  communication  with  the  colon,  and  the  liver 
was  riddled  with  abscesses.  An  examination  of.  the 
pancreas  showed  a  simple  interstitial  pancreatitis. 

Drainage  of  the  common  or  hepatic  duct  may  have  to 
be  performed  for  jaundice  due  to  interstitial  pancreatitis 
where  there  is  absence  or  contraction  of  the  gall-bladder, 
either  owing  to  the  gall-bladder  having  been  removed  at  a 
previous  operation  or  to  its  having  contracted  as  the 
result  of  gall-stone  irritation.  This  is  a  much  less  satis- 
factory operation  than  cholecystenterostomy,  as  drainage 
of  the  common  duct  has  to  be  continued  for  some  length 
of  time  and  the  biliary  fistula  is  a  source  of  great  distress 
to  the  patient.  We  have  had  to  drain  the  common  duct 
in  several  such  cases  where  it  was  impossible  to  relieve  the 
patient  in  any  other  way ;  and  in  one  case  it  necessitated 
the  biliary  fistula  being  continued  for  a  considerable  time. 

This  brings  into  prominence  the  imdesirability  of 
removing  the  gall-bladder  as  a  routine  practice  in  operat- 
ing for  gall-stones,  for  unless  it  is  seriously  damaged  or 
ulcerated,  or  is  the  seat  of  malignant  disease,  or  unless 
there  is  ulceration  or  stricture  of  the  cystic  duct,  removal 
is  quite  unnecessary,  and  we  think  it  better  practice  to 
drain  it  simply  and  not  to  perform  cholecystectomy,  since 
on  some  future  occasion,  should  trouble  develop  in  the 
deeper  ducts  or  in  the  pancreas  and  the  gall-bladder  be 
absent,  it  will  be  impossible,  with  few  exceptions,  to  short- 
circuit  the  obstruction.  Moreover,  after  cholecystotomy 
gall-stones  have  no  greater  tendency  to  re-form  than  they 
have  after  cholecystectomy,  and  should  cholelithiasis 
again  develop,  it  will  be  in  the  common  duct,  a  much 
more  serious  position  than  if  in  the  gall-bladder. 

The  following  case  affords  a  good  example  of  the  advan- 
tage of  sparing  the  gall-bladder  in  operating  for  gall- 
stones : 


456       The  Pancreas:  Its  Surgery  and  Pathology 

Mr.  T ,  aged  forty-five,  was  seen  by  one  of  us  on 

July  27,  1905,  suffering  from  jaundice  and  a  biliary 
fistula.  He  gave  the  history  that  he  had  been  operated 
on  in  October,  1904,  by  a  hospital  surgeon  for  suppurating 
gall-bladder,  but  that  the  wound  had  never  healed  and  a 
biliary  sinus  had  persisted.  He  consulted  a  well-known 
Continental  surgeon,  who  advised  operation.  When 
seen  by  us  he  had  a  temperature  of  100°  F.,  and  looked 
ill.  He  said  that  he  was  subject  to  shivering  attacks. 
His  tongue  was  coated  and  there  was  slight  jaundice. 
A  biliary  fistula  was  present,  which  was  discharging  a 
small  quantity  of  bile  and  pus.  He  had  lost  weight  con- 
siderably. The  urine  showed  a  well-marked  pancreatic 
reaction  and  the  fasces  contained  a  quantity  of  fat  and 
muscle  fibre. 

On  July  28,  1905,  the  abdomen  was  opened  and  the 
gall-bladder  was  separated  from  the  fistula,  which  was 
excised.  The  head  of  the  pancreas  was  hard,  and  evi- 
dently the  seat  of  interstitial  pancreatitis,  which  com- 
pressed the  common  bile-duct.  No  gall-stone  could  be 
felt  in  the  common  or  hepatic  ducts.  The  gall-bladder 
was  therefore  connected  to  the  duodenum  so  as  to  short- 
circuit  the  obstruction.  The  patient  made  a  good  recovery 
and  forthwith  began  to  regain  his  lost  flesh,  the  jaundice 
disappeared,  and  his  skin  soon  assumed  a  healthy  colour. 

He  called  to  report  himself  in  January,  1907,  and  said 
that  he  was  in  perfect  health.  An  opportunity  was  taken 
of  examining  his  urine  some  time  after  the  operation, 
when  it  was  found  to  be  normal  and  to  show  no  traces  of 
the  pancreatic  reaction. 

If  the  common  duct  is  greatly  dilated  it  may  be  possi- 
ble to  make  an  anastomosis  between  it  and  the  duodenum 
so  as  to  short-circuit  the  obstruction  in  the  head  of  the 
pancreas. 

The  following  case  affords  an  example  of  choledoch- 
enterostomy  in  such  a  condition : 

Miss  F ,  aged  twenty-eight,  seen  with  Dr.  G- 


in  June,  1903.  She  gave  the  history  that  four  years' 
previously  she  had  had  typhoid  fever,  since  which  time 
she  had  never  been  well.     A  year  previously  she  had  an 


Chronic  Pancreatitis  457 

attack  of  pain  followed  by  jaundice  with  some  enlarge- 
ment of  the  gall-bladder.     In  January,    1902,   she  was 

operated  on  by  Dr.  G .     No  gall-stones  were  found, 

but  the  head  of  the  pancreas  was  much  enlarged.  Chole- 
cystotomy  was  done  and  the  wound  healed  within  the 
month.  She  made  a  good  recovery  from  the  operation, 
and  was  apparently  well  until  March,  1903,  when  she  had 
a  recurrence  of  the  jaundice  with  sickness  and  pain. 
She  became  very  ill  and  rapidly  lost  flesh.  When  we 
saw  her  together  there  was  some  enlargement  of  the  gall- 
bladder and  a  distinct  cystic  swelling  over  the  pancreas, 
and  the  urine  gave  the  characteristic  pancreatic  reaction. 
On  June  4,  1903,  an  operation  was  performed  by  one  of 
us,  when  a  large  cyst  was  found  on  the  inner  side  of  the 
gall-bladder,  containing  bile  and  pus,  which  was  evidently 
a  dilated  common  bile-duct.  No  gall-stones  were  found, 
but  there  was  some  swelling  of  the  head  of  the  pancreas. 
The  gall-bladder  was  also  distended  and  inflamed,  and  it 
was  drained  by  a  separate  tube.  The  patient  made  a 
good  recovery  from  the  operation,  and  returned  home 
wearing  both  tubes.  She  was  seen  again  in  October,  1903. 
Since  the  former  operation  there  had  continued  to  drain 
away  through  the  tube  in  the  dilated  common  duct  from 
20  to  30  ounces  of  bile,  and  from  the  tube  leading  into 
the  gall-bladder  from  4  to  6  ounces  of  clear  mucus.  The 
patient  was  thin  and  feeble,  had  no  appetite  for  food,  and 
was  unable  to  digest  anything  beyond  a  little  milk.  An 
examination  of  the  urine  revealed  the  characteristic  pan- 
creatic reaction,  and  the  faeces  contained  muscle  fibre 
and  much  fat.  On  the  8th  of  October  a  further  operation 
was  undertaken,  when  the  head  of  the  pancreas  was  again 
found  to  be  much  enlarged,  but  no  concretions  could  be 
felt  in  it  or  in  the  common  bile-duct.  The  gall-bladder 
was  completely  excised  and  the  cystic  duct  ligatured. 
The  dilated  common  bile-duct  was  then  connected  to  the 
duodenum  by  means  of  a  decalcified  bone  bobbin  and  the 
wound  was  closed.  The  same  evening  the  patient  ex- 
pressed herself  as  feeling  hungry  for  the  first  time  since 
her  illness  began.  She  straightway  began  to  absorb 
whatever  nourishment  was  taken,  had  her  bowels  moved 
on  the  second  day,  gained  strength,  resumed  her  natural 
colour,  and  made  such  a  rapid  convalescence  that  she 


458       The  Pancreas:  Its  Surgery  and  Pathology 

returned  home  within  the  month,  having  gained  7  pounds 
in  weight.  In  1906  a  report  was  received  to  say  that  the 
patient  was  in  perfect  health. 

Details  of  the  Operation  for  Exploring  the  Head  of  the 
Pancreas  and  the  Common  Bile-duct. — Certain  modifications 
of  the  operation  for  exploring  the  head  of  the  pancreas  and 
the  common  bile-duct  have  converted  what  was  formerly 
a  most  difficult  procedure,  involving  prolonged  manipula- 
tion, special  appliances,  and  at  least  two  assistants, 
into  a  comparatively  simple  operation,  in  the  greater 
number  of  cases,  requiring  the  help  of  only  one  assist- 
ant and  not  calling  for  the  use  of  any  special  appa- 
ratus. By  this  method,  suggested  and  put  in  practice  by 
one  of  us,  the  time  involved  in  the  operation  is  reduced 
considerably,  and  where  adhesions  do  not  give  unusual 
trouble,  it  is  easy  to  complete  the  work  in  from  thirty  to 
forty  minutes,  which  not  only  means  a  saving  of  time  and 
fatigue  to  the  operator,  but  a  considerable  saving  of 
shock  to  the  patient. 

A  firm  sand-bag  should  be"  placed  under  the  back 
opposite  to  the  liver,  which  not  only  pushes  the  spine, 
and  with  it  the  pancreas  and  common  duct,  forwards, 
but  acts  like  the  Trendelenburg  position  in  pelvic  sur- 
gery by  letting  the  viscera  fall  away  from  the  field  of 
operation,  or  the  same  advantage  may  be  obtained  more 
readily  and  conveniently  by  employing  an  operating 
table  specially  designed  so  as  to  be  able  to  effect  the  pro- 
jection of  the  liver  region  forwards.  The  one  we  regularly 
employ  is  the  Guyose-Greville  table.  A  vertical  incision 
is  then  made  over  the  middle  of  the  right  rectus,  the  fibres 
of  which  are  separated  by  the  finger,  which  is  the  most 
expeditious  and  the  most  effective  method  of  exposing 
the  gall-bladder  and  bile-ducts ;  but  when  it  is  necessary 
to  open  either  the  common  duct  or  the  deeper  part  of  the 
cystic  duct,  instead  of  prolonging  the  incision  downwards, 


Chronic  Pancreatitis  459 

as  was  formerly  done,  it  is  better  to  carry  it  upwards  in 
the  interval  between  the  ensiform  cartilage  and  the  right 
costal  margin  as  high  as  possible,  thus  exposing  the  upper 
portion  of  the  liver  very  freely.  It  will  now  be  found 
that  by  lifting  the  lower  border  of  the  liver  in  bulk,  so  as 
to  rotate  it  if  needful,  first  drawing  the  organ  downwards 
"from  under  cover  of  the  ribs,  the  whole  of  the  gall-bladder 
and  the  cystic  and  common  ducts  are  brought  close  to  the 
surface,  and,  as  the  gall-bladder  is  usually  strong  enough 
to  bear  traction,  the  assistant  can  take  hold  of  it  by  fingers 
or  forceps,  and  by  gentle  traction  can  keep  the  parts  well 
exposed,  at  the  same  time  that,  by  means  of  his  left 
hand  with  a  flat  gauze  sponge  under  it,  he  retracts  the 
left  side  of  the  wound  and  the  viscera,  which  would  other- 
wise fall  over  the  common  duct  and  impede  the  view. 

It  will  now  be  observed  that,  instead  of  the  gall-bladder 
and  cystic  duct  making  a  considerable  angle  with  the 
common  duct,  an  almost  straight  passage  is  found  from 
the  opening  in  the  gall-bladder  to  the  entrance  of  the 
bile-duct  into  the  duodenum,  and  if  adhesions  have  been 
thoroughly  separated,  as  they  should  always  be,  the  sur- 
geon has  immediately  under  his  eye  the  whole  length  of 
the  ducts  with  the  head  of  the  pancreas  and  the  duode- 
num. So  complete  is  the  exposure  that,  if  needful,  the 
peritoneum  can  be  incised,  and  the  common  duct  can  be 
separated  from  the  structures  in  the  free  border  of  the  lesser 
omentum,  but  this  is  not  necessary  except  where  a  growth 
has  to  be  excised.  By  incising  the  peritoneum  passing 
from  the  duodenum  to  the  pancreas,  the  duodenum  can 
be  lifted  up  and  the  posterior  surface  of  the  pancreas  and 
the  common  bile-duct  can  be  fully  exposed.  The  surgeon, 
whose  hands  are  both  free,  can  with  his  left  finger  and 
thumb  so  manipulate  the  common  duct  as  to  render 
prominent  any  concretions,  which  can  be  cut  down  on 
directly,  the  edges  of  the  opening  in  the  duct  being  caught 
by  pressure  forceps.     The  assistant  can  now  take  hold 


460       The  Pancreas:  Its  Surgery  and  Pathology 

of  the  forceps  with  his  left  hand,  as  that  instrument  with 
the  sponge  will  form  a  sufficient  retractor,  since  the  duct 
is  so  near  the  surface.  When  the  duct  is  incised  there  is 
usually  a  free  flow  of  bile,  which,  it  must  be  remembered, 
is.  infected,  but  a  gauze  swab  in  the  kidney  pouch  and  the 
rapid  mopping  up  of  bile  as  it  flows,  by  means  of  sterilized 
gauze  pads,  avoid  any  soiling  of  the  surrounding  parts, 
and,  if  thought  necessary,  the  bulk  of  the  infected  bile  can 
be  drawn  off  by  the  aspirator,  either  from  the  gall-bladder 
or  from  the  common  duct  above  the  obstruction,  before 
the  incision  into  the  duct  is  made.  After  removing  all 
obvious  concretions  the  fingers  are  passed  behind  the 
duodenum  and  along  the  course  of  the  hepatic  ducts  to 
feel  if  other  gall-stones  are  hidden  there,  and  a  gall-stone 
scoop,  the  only  special  instrument  necessary,  is  passed 
up  into  the  primary  division  of  the  hepatic  duct  in  the 
liver  and  quite  down  to  the  duodenal  orifice  of  the  com- 
mon bile-duct,  and  to  ensure  the  opening  into  the  duode- 
num being  patent,  a  long  probe  is  passed  into  the  bowel. 
The  incision  into  the  bile-duct  is  now  closed  by  an  ordi- 
nary curved  round  needle  held  in  the  fingers  without  any 
needle-holder,  a  continuous  catgut  suture  being  used  for 
the  margins  of  the  duct  proper,  and  a  continuous  fine 
green  catgut,  or  spun  celiuloid,  thread  being  employed 
to  close  the  peritoneal  edges  of  the  gut.  In  such  cases, 
where  the  pancreas  is  indurated  and  swollen  from  chronic 
pancreatitis,  and  is  likely  to  exert  pressure  on  the  com- 
mon duct  for  a  time,  a  drainage-tube  is  inserted  directly 
into  the  duct,  and  the  opening  closed  around  it  by  a  purse - 
string  suture,  the  tube  being  fixed  into  the  opening  by  a 
catgut  stitch,  which  will  hold  for  about  a  week ;  but  where 
this  is  not  done,  a  drainage-tube  may  be  fixed  into  the 
fundus  of  the  gall-bladder  in  the  same  way,  as  this  drains 
away  all  infected  bile  and  avoids  pressure  on  the  newly 
sutured  opening  in  the  duct;    or,  better  still,  the  gall- 


Chronic  Pancreatitis  461 

bladder  may  be  short-circuited  into  the  duodenum  by  the 
operation  known  as  cholecystenterostomy. 

vSo  easy  is  it  to  remove  impacted  stones  after  this 
method  of  exposure  that  a  long  time  need  not  be  spent  in 
manipulating  stones  impacted  either  in  the  cystic  or 
common  duct,  but  the  duct  can  be  incised  at  once,  the 
concretions  removed,  and  the  opening  closed  without 
damaging  the  duct  by  prolonged  manipulation.  Although 
there  is  seldom  any  fear  of  leakage  or  of  infection,  yet 
owing  to  the  separation  of  extensive  adhesions,  there  is 
usually  some  tendency  to  pouring  out  of  fluid  in  the  first 
twenty-four  hours.  It  is  therefore  generally  advisable 
to  insert  a  gauze  drain  through  a  split  drainage-tube, 
bringing  it  out  by  the  side  of  the  gall-bladder  drain,  or, 
better  still,  both  tubes  may  be  brought  out  of  a  separate 
opening  external  and  posterior  to  the  operation  wound, 
which  can  then  be  permanently  closed.  The  wound  is 
closed  in  the  usual  way  by  continuous  catgut  sutures, 
first  to  the  peritoneum  and  deep  rectus,  next  to  the 
anterior  rectus  sheath,  and  lastly  to  the  skin.  Even  in 
acute  or  subacute,  as  well  as  in  chronic  pancreatitis, 
this  method  is  advantageous,  as,  at  the  same  time  that 
the  pancreas  is  exposed,  the  bile-ducts  can  be  explored, 
and  if  the  cause  be  gall-stones,  they  can  be  removed. 
Should  it  be  necessary  to  expose  the  under  surface  of  the 
pancreas,  an  extension  of  the  incision  downwards  gives 
enough  room  to  raise  the  transverse  colon  and  to  get 
directly  at  the  body  of  the  pancreas  through  the  trans- 
verse mesocolon. 

To  those  having  little  experience  in  this  operation 
the  modifications  described  may  seem  trivial,  but  to  those 
who  have  experienced  the  difficulties  of  the  ordinary 
operation,  a  method  which  enables  the  pancreas  and  the 
whole  of  the  bile-passages  to  be  dealt  with  close  to  the 
surface  will  be  sufficiently  appreciated.  But  the  tech- 
nique of  the  operation  is  not  the  only  important  part  of  the 


462       The  Pancreas:  Its  Surgery  and  Pathology 

treatment  of  these  serious  cases,  which  require  care  and 
thought,  not  only  before  and  at  the  time  of,  but  subse- 
quently to  operation. 

A  careful  study  of  the  causes  of  mortality  in  operations 
on  the  common  duct,  associated  with  jaundice  and  pan- 
creatitis, shows  that  haemorrhage,  either  immediate,  con- 
secutive, or  secondary,  cannot  be  ignored  as  a  danger, 
and  that  shock,  apart  from  haemorrhage,  has  next  to 
claim  our  attention.  Sepsis  is  no  longer  the  bugbear  that 
it  used  to  be,  thanks  to  a  rigid  all-round  asepsis,  the 
employment  of  gauze  drainage,  and  the  careful  avoidance 
of  soiling  the  wound  by  infected  bile. 

Although  there  is  a  greater  tendency  to  bleeding  in 
chronic  jaundice  from  pancreatic  disease  than  when 
jaundice  is  due  to  gall-stone  obstruction,  there  can  be  no 
doubt  that  in  all  cholasmic  conditions  the  blood  becomes 
so  altered  that  the  coagulability  is  seriously  diminished, 
and  that  these  features  demand  serious  attention  before 
any  operation  is  undertaken  in  cases  of  common-duct 
cholelithiasis.  By  administering  chloride  of  calcium  in 
the  case  of  jaundiced  patients,  both  before  operation, 
in  30-grain  doses  by  the  mouth,  and  afterwards  in 
60 -grain  doses  by  the  rectum  daily  for  several  days,  the 
haemorrhagic  tendency  can  be  successfully  combated. 

It  is  important  to  ligature  all  bleeding  points  and  not 
to  trust  simply  to  forci pressure ;  and,  while  in  non-jaun- 
diced patients  adhesions  may  be  simply  separated,  in 
these  cases  it  is  preferable  to  divide  adhesions  between 
ligatures  where  practicable.  Where  there  is  persistent 
oozing  of  blood  from  innumerable  points,  a  tampon  of 
sterilized  gauze  forms  a  useful  means  of  haemostasis,  and 
this  may  be  made  more  efficient  by  employing  at  the  same 
time  a  solution  of  suprarenal  extract  to  the  bleeding 
surface. 

The  best  treatment  of  shock  is  preventive,  and  to  that 
end  it  is  desirable  to  lose  as  little  blood  as  possible,  though 


Chronic  Pancreatitis  463 

shock  in  operation  is  not  always  dependent  on  loss  of 
blood.  The  patient  is  enveloped  in  a  roughly  made  suit 
of  gamgee  tissue,  and  where  he  is  very  feeble,  or  the 
operation  is  likely  to  be  prolonged,  it  is  performed  on  a 
heated  table.  A  large  enema  of  normal  saline  solution 
with  or  without  stimulant,  given  from  fifteen  to  twenty 
minutes  before,  and  the  administration  of  five  minims 
of  solution  of  strychnia,  subcutaneously  just  after  the 
operation,  are  useful.  Expedition  in  operating  is  an  im- 
portant factor  in  lessening  shock,  especially  in  abdominal 
surgery,  for  it  stands  to  reason  that  prolonged  manipu- 
lation and  exposure  of  the  viscera  in  patients  so  ill  as 
those  composing  the  class  of  cases  which  we  are  now  con- 
sidering must  generally  be,  will  be  badly  borne,  for  it  is 
not  only  the  work  of  the  surgeon  but  the  deep  anaes- 
thesia that  adds  to  the  shock,  since  for  the  operation  to 
be  well  and  expeditiously  performed  the  muscles  must  be 
thoroughly  relaxed. 

After  the  operation  a  pint  of  saline  fluid,  with  one 
ounce  of  brandy,  is  given  by  enema,  and  five  minims  of 
strychnia  are  given  subcutaneously  in  two  hours  and 
repeated  if  desirable.  The  rectal  injection  is  repeated 
in  two  hours,  and  afterwards  every  four  hours  with  an 
ounce  of  liquid  peptonoids  added.  Subcutaneous  in- 
jections of  saline  fluid  or  intravenous  infusion  are  only 
rarely  required. 

Cholecystenterostomy. — The  operation  of  cholecysten- 
terostomy  consists  in  establishing  an  artificial  opening 
between  the  gall-bladder  and  duodenum,  jejunum,  or 
colon,  preferably  the  duodenum,  at  the  part  lying  nor- 
mally close  to  the  gall-bladder. 

Although  the  conception  of  the  operation  occurred 
independently  to  Harley,  Gaston,  and  Nussbatim,  the 
first  operation  was  actually  performed  by  Winniwarter, 
of  Liege,  in  1880,  and  a  case  operated  by  one  of  us  in 


464       The  Pancreas:  Its  Surgery  and  Pathology 

1889   was  the   first   cholecystenterostomy  performed  in 
Great  Britain. 

Since  1889  we  have  performed  the  operation  forty-eight 
times,  and  for  the  following  conditions : 

1.  Interstitial  pancreatitis  compressing  the  common 
bile-duct. 

2.  Biliary  fistula,  due  to  stricture  of  the  common  bile- 
duct,  or  to  compression  of  it  by  a  swollen  and  inflamed 
pancreas. 

3.  Cancer  of  the  head  of  the  pancreas,  where  relief  of 
the  urgent  symptoms  appeared  to  be  desirable. 

A  recent  statement,  to  the  efl:ect  that  cholecystenter- 
ostomy is  a  very  serious  operation  with  a  heavy  mortality, 
is  clearly  incorrect  when  performed  for  non-malignant 
conditions,  if  the  operation  is  properly  carried  out  and 
with  all  necessary  precautions. 

The  following  statistics  shew  the  results  in  our  practice : 

The  operation  has  been  performed  in  thirty-nine  cases 
for  chronic  interstitial  pancreatitis,  with  two  deaths,  and 
in  ten  for  cancer  of  the  pancreas,  with  seven  deaths. 
The  cause  of  death  in  the  two  fatal  cases  of  chronic  pan- 
creatitis was  in  no  way  connected  with  the  operation, 
for  in  one  death  occurred  from  acute  nephritis,  with 
suppression  of  urine  and  ursemic  convulsions,  without 
apparent  cause,  after  the  patient  was  apparently  well 
and  the  wound  had  been  soundly  healed  for  a  week,  and 
in  the  other  there  was,  in  addition  to  the  pancreatitis, 
suppurative  cholangitis  and  abscess  of  the  liver.  The 
very  high  mortality  in  the  cancer  cases  clearly  proves 
that  operative  interference  is  highly  undesirable  and  that 
every  means  should  be  taken  to  diagnose  the  condition 
from  simple  inflammation,  in  which  the  results  following 
operation  are  nearly  always  most  satisfactory. 

It  is  therefore  an  extremely  useful  operation  in  suitable 
cases,  such  as  obstruction  of  the  common  bile-duct  from 
interstitial  pancreatitis,  and  in  biliary  fistula  dependent 


Chronic  Pancreatitis  465 

on  stricture  of  the  common  bile-duct,  but  only  rarely  is  it 
justifiable  to  perform  the  operation  in  cancer  of  the  head 
of  the  pancreas,  as,  at  the  best,  life  in  such  cases  is  not 
considerably  prolonged  by  any  operation.  It  can  rarely 
be  justifiable  or  wise  to  perform  it  in  gall-stone  obstruc- 
tion, as  the  modern  operation  of  choledochotomy,  which 
removes  the  obstruction,  can  be  performed  in  as  short  a 
time  and  is  curative,  whereas  any  short-circuiting  opera- 
tion performed  for  gall-stones  leaves  the  irritating  foreign 
bodies,  which  may  lead  to  other  complications. 

The  anastomosis  ought  unquestionably  to  be  made 
between  the  duodenimi  and  gall-bladder,  as  in  that  way 
the  secretions  mix  with  the  food  in  the  normal  position 
and,  the  duodenum  being  part  of  the  intestinal  canal 
less  frequented  by  organisms  than  the  bowel. lower  down, 
there  is  practically  little  or  no  danger  of  infection  of  the 
bile-passages.  As  a  matter  of  fact,  we  have  never  seen 
infection  to  occur  in  any  case  of  duodeno-gall-bladder 
anastomosis,  but  we  know  of  cases  in  which  an  anasto- 
mosis between  the  gall-bladder  and  colon  has  been  fol- 
lowed after  a  time  by  multiple  abscesses  in  the  liver  and 
death  from  pysemia. 

If  it  should  be  thought  desirable  to  perform  cholecysten- 
terostomy  in  cancer  of  the  head  of  the  pancreas,  it  will 
be  desirable  to  carry  out  the  operation  with  great  expedi- 
tion, and  in  such  a  case  it  may  be  justifiable  to  make  the 
anastomosis  to  the  colon,  or,  better,  to  a  loop  of  the 
jejunum  which  can  be  brought  up  on  the  right  side  of 
the  great  omentum. 

The  late  von  Mikulicz  suggested  an  entero-anastomosis 
of  the  jejunal  loop,  as  shown  in  the  diagram  (Fig.  140), 
but  this  has  never  been  found  necessary  in  our  experience, 
and  as  it  prolongs  the  operation  by  a  few  minutes,  we  do 
not  think  it  should  be  carried  out  in  any  patient  very 
seriously  ill. 

If  the  adhesions  around  the  duodenum  are  not  too 
30 


466       The  Pancreas:  Its  Surgery  and  Pathology 

extensive  so  that  much  time  would  be  occupied  in  detach- 
ing them,  the  operation  of  cholecystenterostomy  may  be 
facilitated  by  Kocher's  method  of  mobilizing  the  duode- 


Fig.  140. — -I,  Anastomosis  of  gall-bladder  with  duodenum;  2, 
anastomosis  of  gall-bladder  with  jejunum;  3,  anastomosis  of  gall- 
bladder with  small  intestine  and  lateral  anastomosis  of  intestine; 
4,  anastomosis  of  gall-bladder  with  colon. 


num.  This  is  effected  by  incising  the  parietal  peritoneum 
of  the  posterior  abdominal  wall  vertically  about  an  inch 
to  the  outer  side  of  the  duodenum ;  by  inserting  the  finger 


Chronic  Pancreatitis 


467 


into  this  sHt,  the  loose  cellular  tissue  in  front  of  the  kid- 
ney is  easily  stripped,  and  the  duodenum  can  be  displaced 
inwards  and,  without  difficulty,  brought  forward  and 
clamped  before  the  anastomosis  is  made,  but,  as  a  rule, 
mobilization  of  the  duodenum  is  unnecessary  if  the  curved 
clamps  (first  invented  by  Sir  Thomas  Smith  for  intestinal 
work  and  shown  in  the  diagram.  Fig.  141)  are  applied  to 
the  duodenum  when  the  patient's  hepatic  region  is  made 
to  bulge  forwards,  either  by  the  special  table  we  use,  or 
by  the  sand-bag  under  the  back. 

Having  grasped  the  fundus  of  the  gall-bladder  and  the 
nearest  part  of  the  duodenum  separately  in  clamps,  the 


Fig.   141. — Intestinal  clamp  employed  in  the  operation  of  cholecyst- 

enterostomy. 


two  viscera  are  approximated  and  the  serous  surfaces 
united  by  a  suture  of  fine  Pagenstecher's  thread  for  at 
least  an  inch,  or  better  li  inches,  in  length;  in  front  of 
this  the  two  viscera  are  incised  to  the  extent  of  an  inch 
and  the  margins  of  the  incision  in  the  two  viscera  are 
united  all  around  by  a  fine  continuous  chromic  catgut 
suture,  after  which  the  Pagenstecher  suture  is  continued 
around  the  front  of  the  circle  outside  the  marginal  suture 
until  it  reaches  the  starting-point,  where  the  two  ends  are 
knotted  and  cut  short. 

The  anastomotic  opening  is  thus  secured  by  a  marginal 
continuous  catgut  suture,  which  unites  all  the  coats  of 
the  two  viscera,  and  an  external  continuous  suture  of 


468       The  Pancreas:  Its  Surgery  and  Pathology 

Pagenstecher's  thread,  which  unites  the  serous  and  sub- 
serous coats  external  to  the  marginal  sutures. 

The  junction  may  be  made  by  a  Murphy  button,  or  by  a 
Mayo  Robson's  decalcified  bobbin,  but  we  prefer  the 
method  of  union  by  suture,  which  is  both  expeditious  and 
effectual. 

The  advantage  of  cholecystenterostomy  in  interstitial 
pancreatitis  is  that  it  provides  for  permanent  drainage  of 
the  bile-passages,  so  that  should  the  inflammatory  tissue 
in  the  pancreas  further  contract  and  cause  increased 
pressure  on  the  bile-duct,  no  jaundice  will  occur,  and 
should  the  inflammatory  process  in  the  pancreas  take 
some  weeks  or  months  to  completely  pass  away,  the 
patient  will  not  be  distressed  by  the  presence  of  a  biliary 
fistula  or  inconvenienced  by  the  absence  during  that  time 
of  the  bile  from  the  intestines;  moreover,  there  will  not 
be  the  anxiety  of  any  further  operation  to  face,  as  there 
would  be  after  a  cholecystotomy.  But,  besides  the  relief 
of  jaundice,  the  operation  acts  on  the  pancreas  by  reliev- 
ing tension  and  thus  enabling  the  gland  to  discharge  its 
contents,  which  when  infected  and  imprisoned  in  the 
ducts,  tends  to  keep  up  infiammation  and  to  lead  after  a 
time  to  atrophy  of  the  gland  substance  proper  and  the 
formation  of  fibrous  tissue. 

It  will  be  gathered  from  the  foregoing  arguments  that 
we  believe  the  operation  of  cholecystenterostomy  to  be 
the  operation  of  choice  for  the  treatment  of  interstitial 
pancreatitis,  and  only  in  case  of  absence  or  contraction 
of  the  gall-bladder,  or  in  case  of  unusual  difficulties  from 
adhesions  or  from  the  serious  condition  of  the  patient, 
would  we  counsel  cholecystotomy  being  done. 

Results. — In  considering  the  after-results  of  the  surgi- 
cal treatment  of  the  class  of  cases  under  consideration 
it  is  necessary  to  give  both  the  immediate  risks  of  opera- 
tion and  the  ultimate  issue  of  those  cases  that  recovered. 
To  this  end  letters  were  addressed  to  the  friends  or  medi- 


Chronic  Pancreatitis  469 

cal  attendants  of  all  patients  who  had  not  recently  been 
heard  of. 

Of  one  hundred  and  two  operations  undertaken  in 
patients  where  chronic  pancreatic  trouble  constituted  the 
chief  disease,  or  where  it  formed  a  serious  complication 
of  other  diseases,  96.1  per  cent,  of  cases  were  followed  by 
recovery,  giving  a  mortality  of  3.9  per  cent.,  but  since 
compiling  the  foregoing  figures,  in  1904,  our  experience 
has  very  largely  increased,  and  the  mortality  has  dimin- 
ished to  a  little  over  2  per  cent. 

Of  the  four  cases  that  died,  one  was  a  cholecystotomy 
undertaken  in  a  patient  very  deeply  jaundiced  and 
reduced  to  the  last  stage  of  exhaustion  before  a  surgical 
opinion  was  sought,  and  where  at  autopsy  a  cirrhotic 
condition  of  the  head  of  the  pancreas  was  found.  The 
second  was  a  cholecystenterostomy  undertaken  in  a 
deeply  jaundiced  patient  in .  the  presence  of  extensive 
adhesions,  which,  on  account  of  the  feeble  condition  of 
the  subject,  seemed  too  formidable  to  deal  with.  In  this 
case  a  necropsy  revealed  a  calculus  in  the  pancreatic  por- 
tion of  the  common  bile-duct,  occluding  the  opening  of 
the  pancreatic  duct,  which  would  have  been  discovered 
had  the  patient's  condition  permitted  a  thorough  ex- 
ploration. A  third  case  was  in  a  very  feeble  patient 
operated  on  away  from  home,  extremely  jaundiced,  and 
suffering  from  repeated  rigors.  Drainage  was  imperfectly 
carried  out,  and  she  died  of  choleemia  two  weeks  later. 
And  a  fourth  case  was  a  choledochotomy  in  an  aged,  feeble 
man,  who  died  of  heart  failure,  accelerated  by  intestinal 
hemorrhage,  in  the  third  week  after  operation,  when  the 
wound  had  healed. 

In  the  fifty-five  cases  of  catarrhal  interstitial  pancrea- 
titis where  gall-stones  were  found  obstructing  the  pan- 
creatic portion  of  the  common  duct,  choledochotomy  was 
performed  in  forty-two,  cholecystotomy  in  nine,  and 
cholecystenterostomy  in  four. 


470      The  Pancreas:  Its  Surgery  and  Pathology 

Of  the  fifty-two  patients  that  recovered,  forty-eight 
were  Hving  and  well  when  last  heard  of ;  one  is  apparently 
well  nine  and  a  half  years  subsequent  to  operation,  though 
sugar  has  recently  been  found  in  his  urine ;  one  died  from 
cirrhosis  of  liver  and  ascites  a  year  after,  it  being  present 
and  far  advanced  at  the  time  of  operation.  Another 
has  since  died  of  acute  bronchitis,  and  another  from 
some  other  non-specified  ailment. 

In  one  case  where  the  cause  was  pancreatic  lithiasis, 
and  where  calculi  were  removed  both  from  Wirsung's 
and  Santorini's  ducts,  the  patient  is  now  in  very  good 
health. 

In  forty-six  cases  of  interstitial  pancreatitis  without 
gall-stones  or  other  removable  cause,  the  bile-ducts,  and 
thus  indirectly  the  pancreatic  ducts,  were  drained  in 
nineteen  cases  by  simple  cholecystotomy,  in  seventeen 
by  cholecystenterostomy,  and  in  five  by  separation  of 
adhesions  and  thoroughly  freeing  the  ducts.  Of  the 
forty-five  patients  that  recovered,  no  reply  to  letters  was 
received  from  six,  who  were  well  some  time  after  operation. 
The  rest  were  in  good  health  when  last  heard  of,  with  the 
exception  of  one  (not  drained)  who  has  developed  glyco- 
suria some  years  after  operation,  but  is  otherwise  well; 
one  who  shows  signs  of  permanent  damage  to  the  pan- 
creas by  the  urinary  test;  and  one  who  has  anaemia 
suggestive  of  the  pernicious  type. 

Besides  the  nineteen  cholecystotomies,  were  five  where 
the  pancreatitis  was  associated  with  duodenal  ulcer,  and 
in  these  cases  a  posterior  gastro-enterostomy  was  per- 
formed at  the  same  time,  with  good  results  in  every  case. 

It  will  thus  be  seen  that  in  a  very  large  percentage  of 
cases  the  removal  of  the  cause,  together  with  drainage 
of  the  bile-ducts,  or,  in  the  absence  of  a  removable  cause, 
the  simple  drainage  of  the  bile-ducts  alone,  is  an  opera- 
tion that  may  be  safely  recommended  in  suitable  cases 
that  have  failed  to  yield  to  general  treatment. 


Chronic  Pancreatitis  471 


Literature 

Adams:  Lancet,  Dec.  9,  1905. 

Anders:    North.  Med.  Soc.  of  Phila.,  Jan.  5,  1904. 

Ansperger:   Rev.  de  Chirurg.,  Oct.  10,  1905. 

Barling:    Brit.  Med.  Journ.,  Feb.  24,  1905;    Ibid.,  April  25,  1903. 

Barnard:   Clin.  Journ.,  June  14,  1905. 

Boeckmann:   St.  Paul's  Med.  Journ.,  Jan.,  1904. 

Bosanquet:   Lancet,  i,  1904. 

Bottersby:   In  Fauconneau-Dufresne,  1856. 

Carnot:  Thesis,  Paris,  1898. 

Chalmers:   Journ.  of  Ceylon  Tr.  Brit.  Med.  Assoc,  i,  2,  1904. 

Cotter:   Brit.  Med.  Journ.,  May  5,  1906. 

Dalziel:   Brit.  Med.  Journ.,  1902. 

Davian:   Thesis,  Paris,  1906. 

Deaver:  North.  Med.  Soc.  of  Phila.,  Jan.  5,  1904;  Amer.  Journ.  of  Med. 

Sci.,  Feb.,  1903. 
Deaver  and  Miiller:  Amer.  Med.,  March  19,  1904. 
Delbet:   Cong,  franc,  de  Chir.,  1902. 
Desjardins:    Thesis,  Paris,  1905. 
Ehler:    Wiener  klin.  Wochen.,  Dec.  17,  1903. 
Estes:  Journ.  Amer.  Med.  Assoc,  Oct.,  1902. 
Evans:  Journ.  Amer.  Med.  Assoc,  1901. 
Fitz:  AUbutt's  "System  of  Medicine,"  iv,  264. 
Gamges:   Midland  Med.  Soc,  Feb.  17,  1904. 
Giordano:  Thesis,  Perrin,  Lyons,  1902. 
Gosset:  Thesis,  Desjardins,  1905. 
Hardin:    Med.  Bull.,  Quebec,  1904. 
Jaboulay:   Lyon  medical,  1898. 
Kehr:  "Technic  des  Gallensteinoperationen,"  1905;  Munchener  medic. 

Woch.,  April  5,  1904;  XXXIII.  Kong.  d.  D.  gesellsch.  f.  Chir., 

1904. 
Klippel  and  Lefas:  Arch.  gen.  de  Med.,  July,  1899;   Ref.  de  Med.,  Jan. 

10,  1903. 
Korte:  Chir.  des  voies  billiares,  1905;  Deutsche  Chir.,  1898;  Centralbl. 

f.  Chir.,  27,  1904. 
Lejars:  Cong,  de  Chir.,  Paris,  1905. 
Lowe:  Brit.  Med.  Journ.,  Feb.  27,  1904,  p.  493. 
Mahomed:   Brit.  Med.  Journ.,  July  2,  1904. 
Marcy:  Journ.  Amer.  Med.  Assoc,  Oct.,  1902. 
Mayo:   Med.  News,  June  11,  1904. 
Megnin   and   Nocard:     Friedberger  and   Frohner's   "Vet.   Path.,"   tr. 

Hayes,  1905. 
Moore:  Lancet,  July  2,  1904. 

Mosetig-Moorhof :   Wiener  med.  Presse,  Jan.,  1902. 
Moynihan:    Lancet,  June  6,  1903;     Brit.  Med.  Journ.,  Dec.  31,  1904; 

Edinb.  Med.  Journ.,  May,  1906. 
Myles:    Brit.  Med.  Journ.,  1902. 
Opie:    "Diseases  of  the  Pancreas,"  1903. 
Oser:    "Nothnagel's  Encyclop.  of  Pract.  Medicine." 
Owen:   Brit.  Med.  Journ.,  1902,  p.  1310. 
Qu^nu:   Bull.  Soc.  Chir.,  March  7,  1905. 
Quenu  and  Duval:   Rev.  de  Chir.,  Oct.  10,  1905. 
Raven:   Brit.  Med.  Journ.,  Oct.  15,  1904. 
Raynds:   Quoted  Villar,  Cong,  of  Surgery,  Paris,  1905 
Riedel:   Berl.  klin.  Woch.,  i,  1896. 


472       The  Pancreas:  Its  Surgery  and  Pathology 

Robson,  Mayo:  Lancet,  July  28,  1900;  Philadelphia  Med.  Journ., 
June  I,  1901;  Lancet,  March  19,  26,  April  2,  1904.  Montreal 
Med.  Journ.,  Nov.,  1904;  Lancet,  Dec.  23,  1905;  Edin.  Med. 
Jour.,  Dec,  1905;  Surgery,  Gynecology,  and  Obstetrics,  Jan., 
1906. 

Rodocanachi :   Lancet,  July  7,  1906. 

Schmieden:  Miinch.  med.  Woch.,  1906. 

Segond:  Soc.  de  Chir.,  Feb.  14,  1906. 

Sendler:   Deut.  Zeit.  f.  Chir.,  1896,  1897. 

Senn:  Trans,  of  the  Amer.  Surg.  Assoc,  Phila.,  1886. 

Terrier:    Soc.  de  Chir.,  Feb.  7,  1906;    quoted  Desjardins,  Thesis,  1905. 

Tuffier:    Bull,  et  Rev.  de  la  soc  de  Chir.  de  Paris,  xxxvi,  1905. 

Walther:  Quoted  by  Desjardins,  Thesis,  1905. 

White,  Hale:  Brit.  Med.  Journ.,  July  iS,  1903;  Guy's  Hosp.  Rep., 
liv,  17. 

Wiener:  Quoted  by  Quenu  and  Duval. 

Zeller:   Berliner  klin    Woch..  1902. 


CHAPTER  XVII 

PANCREOLITHIC  CATARRH  AND  PANCREATIC 
CALCULI 

Pancreatic  calculi  are  exceedingly  rare.  Two  cases 
were  observed  by  Panarol  and  Galea  in  1667,  one  by 
Morgagni  in  1765,  and  Cowley,  in  1788,  referred  to  an 
instance  observed  by  himself.     ]\Iatthew  Baillie,  physi- 


%% 


Fig.  142. — Pancreatic  lithiasis  (Baillie). 


cian  to  St.  George's  Hospital,  in  a  work  on  "Morbid 
Anatomy,"  published  in  1799,  figures  a  case  of  pancreatic 
calculi  most  carefully  dissected  and  showing  the  relation 
of  the  bile-duct  and  pancreatic  duct  (Fig.  142). 

473 


474       The  Pancreas:  Its  Surgery  and  Pathology 


In  1883  Johnston  collected  the  notes  of  thirty-five 
recorded  cases.  The  fullest  account  was  given  in  1896  by 
Guidiceandrea  and  was  based  upon  forty-eight  recorded 
cases  and  two  observed  by  the  author.  Others  have  since 
been  reported,  but  they  are  so  uncommon  that  Oser  said 
there  were  in  1903  only  seventy  recorded  cases.  We 
have  been  able  to  collect  others  described  since  that  date, 

and  not  included  in  that  series, 
but  doubtless  there  are  many  un- 
recorded. The  subject  of  pancre- 
atic concretions  can  never  assume 
the  importance  that  attaches  to 
cholelithiasis,  but  as  pancreatic 
calculi  are  associated  with  serious 
and  usually  progressive  disease  of 
the  gland,  and  as  they  can  be  re- 
moved by  operation,  their  recog- 
nition and  treatment  are  matters 
that  demand  some  consideration. 

Calculi  are  never  found  in  a 
healthy  pancreas,  and  it  seems 
highly  probable  that,  like  gall- 
stones, pancreatic  concretions  are 
the  result  of  catarrh  of  the  ducts 
with  stagnation  of  secretion,  which 
generally,  if  not  always,  results 
from  infection.  Instead  of  calculi 
being  formed,  the  ducts  may  actu- 
ally be  lined  with  calcareous  mate- 
rial that  may  accumulate  so  much  as  to  close  completely, 
or  almost  completely,  the  lumen.  An  example  of  this, 
taken  from  a  specimen  in  the  University  College  Hospital 
Museum  (Fig.  143),  illustrates  this  condition.  It  will 
be  noticed  that  the  duct  of  Wirsung  is  widely  dilated  and 
that  it  also  contains  calculi. 

An  interesting  case  in  which  the  head  of  the  pancreas 


Fig.  143. — Calcifica- 
tion of  the  duct  of  Wir- 
sung with  atrophy  of  the 
pancreas  (Univ.  Coll. 
Hosp.    Museum,    3197). 


Pancreolithic  Catarrh  and  Pancreatic  Calculi    475 

was  infiltrated  with  calcareous  material  has  been  reported 
by  Delageniere.  The  patient  was  a  man  of  fifty-nine, 
who  complained  of  violent  epigastric  pains  followed  by 
increasing  jaundice.  At  operation  the  gall-bladder  was 
foiind  to  be  distended  and  to  contain  a  biliary  calculus. 
A  resistance  was  felt  in  the  region  of  the  common  duct 
which  was  thought  to  be  a  large  calculus,  but,  on  careful 
examination,  it  was  found  to  be  a  hardening  of  the  head 
of  the  pancreas  around  the  common  duct.  On  making 
an  incision  into  the  affected  area  it  was  found  to  be  densely 
infiltrated  with  small,  hard,  calcareous  granules,  15  grams 
of  which  were  removed  with  a  ciurette.  The  cavity  thus 
formed  was  drained  and  the  patient  eventually  made  a 
good  recovery,  being  relieved  of  his  symptoms  and  able 
to  return  to  work.  Microscopical  examination  of  the 
material  removed  at  operation  showed  that  it  consisted 
of  pancreatic  tissue  infiltrated  with  calcium  salts  which 
formed  hard,  yellowish-white  granules,  mostly  of  the 
same  size,  but  in  some  instances  agglomerated  to  form 
larger  masses. 

The  composition  of  pancreatic  calculi  is  important 
from  the  diagnostic  point  of  view,  for  they  contain  lime, 
either  in  the  form  of  carbonate  or  phosphate,  or,  as  in 
one  case  reported  by  Mr.  Shattock,  of  oxalate,  which 
latter  was  found  in  a  cyst. 

Johnston  gives  two  analyses  of  pancreatic  calculi : 

I 

Phosphorus  salts 72.30 

Carbon  salts 18.90 

Organic  matter 8.80 

II 

Carbon  salts 91-65 

Magnesium  carbonate 4.15 

Organic  matter 3.00 

J.  A.  Milroy  reported  as  follows  on  a  pancreatic  calculus 
removed  by  Moynihan:  "The  stone  contains  nearly  50 
per  cent,  of  calcium  carbonate,     A  small  portion  of  the 


476       The  Pancreas:  Its  Surgery  and  Pathology 


solution  in  which  the  magnesium  was  estimated  was 
unfortunately  used  for  qualitative  testing,  so  that  I  can- 
not state  the  exact  quantity  of  magnesium  present. 
These  were  the  only  inorganic  substances  found.  I  was 
somewhat  surprised  to  find  phosphates  absent.  The 
organic  substances  consisted  almost  entirely  of  proteid. 
Traces  of  organic  substance  soluble  in  alcohol  and  ether 
were  present.  In  the  residue  from  the  alcoholic  and 
ethereal  solutions  cholesterin  and  fat  were  the  only  bodies 

identified.  Purin 
bases  and  uric 
acid  were  absent. 
The  quantity  of 
the  original  pow- 
Jtk  -^H^  der     was    rather 

^BP     >^i1.'"'  Wr  too   small   to   al- 

low of  an  accurate 
estimation  of  the 
constituents." 

In  examining 
the  urine  of  cases 
suffering  from 
chronic  pancrea- 
titis, oxalate  of 
lime  crystals 
have  been  found 
in  over  40  per  cent,  of  our  cases.  In  jaundiced  cases  in 
which  the  bile  acids  take  up  the  lime  salts  they  have 
been  found  only  in  6  per  cent,  of  cases.  It  would  be  inter- 
esting to  know  if  this  fact  has  any  bearing  on  the  compo- 
sition of  pancreatic  concretions,  for  it  is  a  well-known 
fact  that  the  normal  pancreatic  secretion  contains  no  cal- 
cium carbonate.  The  subject  is  worthy  of  further  investi- 
gation. 

The  consequence  of  their  chemical  composition  is  that 
pancreatic  calculi  are  opaque  to  the  ^-rays,  and  in  this 


Fig.  144. — Gall-stones  and  pancreatic  calculi. 


Pancreolithic  Catarrh  and  Pancreatic  Calculi    477 


way  we  have  a  means  of  diagnosing  their  presence  and  of 
differentiating  them 
from  gall-stones, 
which  are  not  seen 
in  a  skiagram.  An 
;\;-ray  photograph  of 
concretions  taken 
from  a  case  where  at 
the  same  time  gall- 
stones and  pancreatic 
calculi  were  removed 
by  one  of  us  is  shown 
in  the  figure  (Fig. 
145),  and  for  com- 
parison an  ordinary 
photograph  of  the 
two  classes  of  con- 
cretions together  is 
also  shown  (Fig.  144). 
in  the  skiagram  is  readily  seen.     The  next  photograph, 


'm 


Fig.  145. — .T-Ray  photograph  of  the 
pancreatic  calcuU  and  gall-stones  shown 
in  Fig.  144,  showing  that  the  former  are 
opaque  to  the  rays. 

The  difference  in  their  appearance 


,.^^ 


Fig.  146. — Skiagram  of  pancreas  containing  calculi;  vessels  injected. 


taken  by  Dr.  J.  Mackenzie  Davidson,   shows  the  calculi 
in  situ,  and  as  the  vessels  have  been  injected  they  also 


478       The  Pancreas:  Its  Surgery  and  Pathology 


show  distinctly. 


So  far  as  we  are  aware,  this  method  of 
diagnosis  was  suggested  for 
the  first  time  by  one  of  us 
in  the  Hunterian  Lectures 
delivered  at  the  Royal  Col- 
lege of  Surgeons  in  March, 
1904. 

By  means  of  this  and  the 
urinary  pancreatic  reaction 
it  will  probably  be  possible 
to  confirm  the  diagnosis  by 
demonstrating  the  associ- 
ated chronic  pancreatitis. 


Fig.  147. — A  pancreas,  with  cal- 
culi of  various  sizes  in  its  ducts, 
which  are  dilated  (Museum  R.  C.  S., 
specimen  No.  2833). 


Fig.  148. — Some  of  the  larger 
calculi  from  the  specimen  shown 
in  Fig.  147  (Royal  Coll.  of  Surg. 
Museum,  2834). 


The  stones  are  rounded,   ovoid,   or  elongated  like   a 
date-stone.     They  are  found  in  all  parts  of  the  ducts  of 


Pancreolithic  Catarrh  and  Pancreatic  Calculi    479 

the  pancreas,  though  much  more  frequently  in  the  head ; 
in  the  tail  of  the  gland  they  are  rarely  seen.  The  calculi 
may  be  branched  like  coral,  the  trunk  of  the  stone  lying 
in  the  main  ducts  and  its  offshoots  in  the  secondary 
ducts,  but  they  are  usually  smooth.  Shupmann  has 
recorded  a  calculus  measuring  2^  inches  by  ^  inch  and 
weighing  200  grains,  and  Matani  has  reported  one  weigh- 
ing 2  ounces.  In  colour  they  are  pale  and  they  may  be 
white,  but  if  they  pass  into  the  common  bile-duct  they 
receive  a  covering  of  cholesterin  and  may  be  stained  by 
the  bile  so  as  to  look  like  gall-stones. 

Concretions,  consisting  chiefly  of  carbonate  of  lime, 
are  sometimes  found  in  the  pancreatic  ducts  of  cattle. 
They  vary  in  size  from  a  millet-seed  to  a  hazelnut  and 
are  white,  cylindrical,  angular,  or  facetted.  The  duct 
and  its  chief  tributaries  are  generally  dilated  like  a  string 
of  beads  and  its  walls  are  thickened. 

Symptoms. — The  symptoms  depend  on  the  associated 
condition,  whether  that  be  cyst,  abscess,  chronic  inflam- 
mation, or  other  pathological  state;  doubtless  in  some 
cases  symptoms  are  vague,  or  even  wanting,  and  in  some 
cases  pancreatic  calculi  have  only  been  discovered  post- 
mortem. Pains  at  the  epigastrium  radiating  towards  the 
inferior  angle  of  the  left  scapula,  often  agonising  in  charac- 
ter and  associated  with  vomiting,  may  be  present,  and 
the  attacks  may  be  brought  on  by  exertion,  or  they  may 
be  irregular,  coming  on  at  any  hour,  day  or  night.  The 
pain  frequently  comes  in  sharp  colicky  attacks,  similar 
to,  but  less  severe  than,  those  due  to  gall-stones.  A  sense 
of  soreness  or  stiffness  is  noticed  for  a  day  or  two  after  the 
attack.  When  the  pain  is  at  its  height,  vomiting,  hiccough, 
rigors,  cold  sweats,  or  collapse  may  be  noticed.  After 
the  attack  some  fragments  of  stone  may  be  found  in  the 
motions  (Minnich,  Leichtenstern,  Kinnicutt).  That  pan- 
creatic colic  is  associated  with  the  passage  of  stones  down 
the  ducts  seems  clearly  to  be  proved  by  the  cases  observed 


480       The  Pancreas:  Its  Surgery  and  Pathology 


at  different  times  by  Minnich  and  Holzmann,  for  it  was 
only  after  each  attack  that  fragments  of  stone  were  found 

in  the  motions. 

Dyspepsia  and 
flatulence  are 
usually  present. 
Liporrhoea  and 
azotorrhoea,  as 
well  as  bulky 
pale  motions, 
are  present 
where  there  is 
well-marked  in- 
terstitial pan- , 
creatitis,  and  in 
some  cases 
where  the  inter- 
stitial changes 
have  advanced 
to  atrophy  or 
fatty  degenera- 
tion of  the  whole 
gland,  glyco- 
suria is  found. 

Glycosuria 
was    recorded 
by    Lancereaux 
in  twelve  out  of 
forty  cases,  but 
his  statement 
that  in  each  at- 
tack   of     colic 
there  is  a  tem- 
porary glycosuria  has  not  been  borne  out  by  the  experi- 
ence  of   subsequent   observers.     The   presence  of  sugar 
may  be  observed  at  intervals.      Holzmann  found  it  in- 


Fig.  149. — Pancreatic  lithiasis  (Leeds  Museum). 


Pancreolithic  Catarrh  and  Pancreatic  Calculi    481 


termittently  in  his  case,  but  while  the  same  patient  was 
under  Minnich's  observation  at  an  eariier  date,  no  sugar 
was  found,  though  regularly  sought.  Caparelli  records 
the  case  of  a  woman  who  developed,  after  many  attacks 
of  acute  epigastric  colic,  an  abscess  above  the  umbilicus. 
The  abscess  burst  and  discharged  some  pus  and  gritty 
material.  Through  the  fistula,  which  persisted  for  six 
years,  many  small  stones,  over  one  hundred  in  all,  were 
expelled.  After  the  spontaneous  closure  of  the  fistula, 
diabetes  developed  and  the  patient  died. 

The  pancreatic  re- 
action in  the  urine 
was  well  marked  in  a 
case  operated  on  by 
one  of  us,  to  be  re- 
ferred to  subsequently, 
and  it  will  probably  be 
generally  found.  If  a 
calculus  descends  into 
the  ampulla  of  Vater, 
jaundice  will  ensue 
and  the  case  will  prob- 
ably be  diagnosed  as 
one  of  gall-stones  in 
the  common  duct,  but 
the  pancreatic  reac- 
tion and  the  use  of  the  x-rsiys  should  enable  a  differential 
diagnosis  to  be  made. 

In  a  case  recorded  by  Korte  a  patient  sufi:ered  from 
biliary  colic  for  which  the  abdomen  w^as  opened.  A  large 
calculus  was  removed  from  the  gall-bladder,  which  was 
drained.  While  the  bile  was  still  discharging  the  patient 
experienced  an  attack  of  pain  similar  to  that  for  which 
operation  had  been  undertaken.  After  death  a  tumour 
in  the  head  of  the  pancreas,  which  during  life  had  been 
31 


Fig.  150. — Section  of  the  fibrosed 
pancreas  in  a  case  of  pancreatic  lithiasis 
(X  ca  40). 


482       The  Pancreas:  Its  Surgery  and  Pathology 

diagnosed  as  malignant,  was  found  to  be  an  abscess  with 
large  concretions  in  it. 

Kummell  records  an  almost  exactly  similar  case  in 
which  cholecystotomy  had  been  performed ;  pain  recurred, 
and  at  the  necropsy  a  large  soft  calculus  was  found  in 
the  canal  of  Wirsung.  Kinnicutt  reports  an  interesting 
case  in  a  woman,  aged  forty-two,  who  had  had  three 
attacks  of  sudden  severe  pain,  beginning  in  the  back  and 
running  around  the  right  side  along  the  lower  intercostal 
spaces,  with  nausea  and  vomiting.  After  an  interval  of 
eight  months,  another  extremely  severe  attack  occurred. 
The  pain  began,  as  before,  in  the  back  between  the  scapulae, 
but  on  this  occasion  it  ran  through — not  around — into 
the  epigastrium,  and  became  localised  to  the  right  of  the 
middle  line.  On  the  sixth  day  after  the  commencement 
of  the  attack  six  small  stones,  the  size  of  a  pea,  were  passed 
per  rectum.  Four  of  these  were  analysed  and  found  to 
be  composed  of  carbonate  and  phosphate  of  lime  with  no 
trace  of  cholesterin  or  bile-pigment,  thus  indicating  their 
origin  in  the  pancreatic  ducts.  Similar  stones,  or  detritus 
of  similar  composition,  were  recovered  from  the  stools 
during  more  than  one  subsequent  attack  of  colic.  Some 
of  the  patient's  later  attacks  were  associated  with  jaundice 
and  on  one  occasion  two  typical  gall-stones  were  recovered 
from  the  stools.  This  case,  the  author  points  out,  shows 
the  difficulty  there  is  in  distinguishing  between  the  pres- 
ence of  biliary  and  pancreatic  calculi.  There  is  nothing 
distinctive  in  the  nausea,  vomiting,  diarrhoea,  character 
of  pain,  or  jaundice.  The  points  which  are  helpful  are 
an  rjc-ray  photograph,  the  finding  of  the  calculus  and  its 
analysis,  glycosuria,  and  a  deficient  splitting  of  ingested 
fats  into  fatty  acids  and  soaps.  In  the  case  described 
fat-absorption  was  normal,  but  of  the  fat  recovered  from 
the  faeces  42.6  per  cent,  was  in  the  form  of  neutral  fat. 

Treatment. — ^According  to  the  results  of  the  experi- 
mental work  of  Kiihne  and  Lea,  the  subcutaneous  in- 


Pancreolithic  Catarrh  and  Pancreatic  Calculi    483 

jection  of  pilocarpine  incites  the  flow  of  the  pancreatic 
juice  but  the  treatment  of  pancreatic  calculi  by  sialagogues 
is  probably  useless  and  mere  waste  of  time,  although 
in  a  case  reported  from  Eichhorst's  clinic  of  "undoubted 
pancreatic  lithiasis,"  in  which  subcutaneous  injections  of 
pilocarpine  were  tried,  "the  attacks  of  colic  disappeared 
completely  and  the  patient  was  better  than  for  many 
months  before." 

Relief  to  pain  may  be  given  by  sedatives,  and  other 
treatment  must  be  adopted  as  occasion  arises,  but  as  soon 
as  pancreatic  stones  can  be  diagnosed,  they  should  be 
removed,  as  destruction  of  the  pancreas  is  otherwise 
certain,  and  it  is  quite  clear  that  medical  treatment  can 
do  no  real  good  in  these  cases. 

Surgical  treatment  has  until  quite  recently  been  merely 
palliative,  but  fortunately  surgery  can  now  offer  a  rea- 
sonable hope  of  cure.  The  pancreatic  duct  can  be  readily 
explored  by  an  incision  in  the  second  part  of  the  duodenum, 
and  by  then  laying  open  the  biliary  papilla  the  opening 
of  Wirsung's  duct  can  be  seen.  From  this  a  probe  can 
be  passed  two  inches  along  the  duct  to  explore  it,  and  by 
this  method  we  have  removed  a  pancreatic  calculus  from 
the  duodenal  end  of  the  duct. 

A  very  exhaustive  search  through  English  and  foreign 
literature  has  only  resulted  in  the  discovery  of  five  opera- 
tions for  pancreatic  calculi.  ]\Ir.  A.  Pearce  Gould's  case, 
operated  on  March  3,  1896,  died  on  the  twelfth  day  from 
exhaustion.  In  Dr.  Dalziel's  case  a  stone  of  the  size  of  a 
very  large  pea  was  removed  from  the  pancreatic  duct 
through  an  incision  in  the  duodenum,  the  opening  in  the 
duct  being  stitched  to  the  wound  in  the  posterior  wall  of 
the  duodenum.  As  the  bile-duct  was  clear  there  was  no 
jaundice.  A  good  recovery  followed.  In  Mr.  B.  G.  A. 
Moynihan's  case  a  pancreatic  stone  was  removed  from  the 
ampulla  of  Vater  through  an  incision  in  the  duodenum 
and  the  patient  recovered.     In  Dr.  L.  W.  Allen's  case  two 


484       The  Pancreas:  Its  Surgery  and  Pathology 


calculi  were  removed  from  a  cyst  between  the  lesser 
curvature  of  the  stomach  and  the  liver.  The  patient 
died  on  the  fifth  day  after  operation. 

In  a  case  which  came  under  the  care  of  one  of  us  on 
February  13,  1903,  four  calculi  were  removed  from  a 
woman  aged  fifty-seven,  one  from  the  duct  of  Santorini, 
or  one  of  its  branches,  by  direct  incision  into  the  pancreas 
close  to  the  common  duct,  afterwards  closing  the  opening 
by  deep  and  by  peritoneal  sutures ;  the  second  and  third 

stones  were  reached 
through  an  incision 
in  the  duodenum 
by  laying  open  the 
papilla,  when  by 
means  of  fine  for- 
ceps a  calculus  was 
removed  out  of  Wir- 
sung's  duct,  along 
which  a  probe  was 
afterwards  passed 
for  two  inches,  and 
a  fourth  concretion 
was  rem.oved  by  di- 
rect pancreatotomy 
from  the  middle  of 
the  duct  of  Wirsung, 
the  stone  being  reached  by  incising  the  gastro-hepatic 
omentum,  drawing  the  stomach  downwards,  incising  the 
pancreas  freely,  and  opening  the  duct  directly  on  to  the 
stone,  which  was  of  the  size  of  a  small  bean.  The  duct 
was  then  closed  with  catgut,  the  wound  in  the  body  of  the 
pancreas  being  sutured  so  as  to  leave  no  dead  space  and 
the  peritoneal  wounds  being  closed  without  direct  drain- 
age. The  right  kidney  pouch  was  then  drained,  as  some 
infected  bile  had  escaped.  Recovery  was  ultimately  com- 
plete. In  this  case  pain  and  vomiting  were  marked  features 


Fig.  151. — Pancreas  showing  calculi  in 
the  duct  of  Wirsung  (St.  George's  Hosp. 
Museum,  203). 


Pancreolithic  Catarrh  and  Pancreatic  Calculi    485 

and  the  pancreatic  reaction  was  of  the  utmost  importance 
from  the  point  of  view  of  diagnosis.  This  is,  apparently, 
the  first  case  in  which  either  the  duct  of  Wirsimg  or  the 
duct  of  Santorini  has  been  deliberately  opened,  and,  after 
the  removal  of  a  calculus,  closed  by  a  suture. 

The  Operation  of  Pancreo-lithotomy. —  For  the  purpose 
of  removing  calculi  from  the  pancreas  an  incision  3  or  3^ 
inches  to  the  right  of  the  middle  line  will  be  found  the 
most  convenient,  as  the  fibres  of  the  right  rectus  can  be 
split  and  the  incision  lengthened  upwards  and  downwards 
without  unnecessarily  weakening  the  abdominal  wall. 
A  sand-bag  under  the  lumbar  spine  will  bring  the  gland 
several  inches  nearer  the  surface.  If  the  opening  of  the 
duct  of  Wirsung  has  to  be  explored,  the  second  part  of 
the  duodenum  may  be  incised  and  the  papilla  common 
to  the  bile-duct  and  pancreatic  duct  laid  open,  when  the 
edges  of  the  opened  diverticulum  of  Vater  can  be  seized 
with  small  catch  forceps  and  drawn  to  the  surface;  a 
probe  or  fine  forceps  can  then  be  readily  passed  into  Wir- 
sung's  duct  and  any  concretion  removed.  If  the  calculi 
are  more  deeply  placed  in  the  ducts,  the  pancreas  may  be 
exposed  either  through  the  gastro-hepatic  omentum  by 
drawing  the  stomach  downwards,  or  by  lifting  the  stom- 
ach it  may  be  reached  through  a  slit  in  the  omentum 
or  by  raising  the  colon,  by  a  slit  in  the  transverse  meso- 
colon ;  or  by  peeling  the  duodenum  from  the  parietes  the 
back  of  the  pancreas  may  be  readily  reached.  The  calculi 
may  be  then  cut  down  on  and  extracted  by  a  scoop  or 
forceps.  Any  bleeding  must  be  arrested  by  ligatures. 
The  duct  can  be  sutured  and  the  incision  in  the  gland 
must  be  brought  together  by  buried  sutures,  the  periton- 
eal covering  being  coapted  by  a  continuous  suture.  If 
leakage  is  feared  a  gauze  drain  may  be  applied,  but  the 
position  may  be  difficult  for  this,  and  if  it  has  to  be  done 
the  gauze  must  be  surrounded  by  a  rubber  drainage-tube 
and  brought  through  it  to  the  surface.     In  the  case  of 


486       The  Pancreas:  Its  Surgery  and  Pathology 

pancreo-lithotomy  above  referred  to  the  closure  of  the 
gland  was  so  secure  as  not  to  require  gauze  packing,  and 
the  result  justified  its  not  being  used.  When  the  duode- 
num is  opened  it  must  be  closed  in  the  usual  way  by  a 
muco-muscular  and  serous  suture,  the  latter  being  of  fine 
celluloid  thread.  The  incised  papilla  need  not  be  sutured. 
If  a  calculus  be  felt  in  the  head  of  the  gland,  but  not  in 
the  duct  of  Wirsung,  it  may  be  reached  by  incising  the 
peritoneum  over  the  duodenum  and  separating  it  gently 
from  the  head  of  the  pancreas,  or  if  more  deeply  placed 
near  the  back  of  the  gland  the  reflection  of  peritoneum 
from  the  duodenum  to  the  abdominal  wall  may  be  incised 
and  the  duodenum  may  then  be  displaced  inwards,  when 
the  back  of  the  pancreas  will  be  exposed,  and,  if  thought 
advisable,  it  may  be  incised  and  treated  as  in  the  incision 
from  the  front. 

Literature 

Allen:   Annals  of  Surgery,  1903,  p.  741. 

Ancelet:    "Etudes  sur  les  mal.  des.  Pancreas,"  Paris,  1864. 

Baillie:   "Morbid  Anatomy,"  1799. 

Caparelli:  Arch.  ital.  de  Biol.,  1894,  xxi,  398. 

Cowley:   Lond.  Med.  Journ.,  1788. 

Dalziel:   Privately  communicated. 

Delageniere:   Arch.  Provinc.  de  Chirurg.,  4,  5,  1906. 

Eichhorst:  Eulenberg's  Realencyklop.,  ii. 

Gaeia:   Graaf,  "De  succo  pancreat.,"  1667. 

Guidiceandra :   II  Policlinico,  1896. 

Gould:   Anat.  Museum  of  Boston,  1847,  P-  ^47- 

Gould,  Pearce:  Trans.  Clin.  Soc.  of  Lond.,  1896. 

Graaf:   "Opera  omnia,"  1667. 

Holzmann:  Miinchener  med.  Wochenschr.,  1894,  Nr.  20. 

Johnston:   Amer.  Journ.  of  Med.  Sci.,  1883. 

Kinnicutt:   Amer.  Journ.  of  Med.  Sci.,  1902,  cxxiv,  948. 

Korte:   Berliner  Klinik,  Dec,  1896. 

Lancereaux:   Journ.  de  med.  enterne,  Feb.,  1889. 

Leichtenstern :      "Handb.    d.    spec.    Therap.    v.    Penzoldt-Stintzung," 

1896,  iv,  203. 
Matani:   Giorn.  di  med.  Venezic,  iv,  174. 
Minnich:   Berliner  klin.  Wochenschr.,  1894,  S.  187. 
Morgagni:   "Opera  omnia,"  iii,  68,  i. 
Moynihan:   Lancet,  Aug.  9,  1902,  p.  355. 
Oser:   Nothnagel's  "Encyclop.  of  Pract.  Med." 
Panarol:   Jatzologismorium,  Roma,  1652,  p.  51. 
Park,  Roswell:   Amer.  Med.,  1903,  v,  949. 

Phillipps:  Brit.  Med.  Journ.,  Feb.  20,  1904;  Clin.  Soc.  Trans.,  1904. 
Robson,  Mayo:  Hunterian  Lectures,  Lancet,  March  19,  26,  April  2,  1904. 
Shattock:  Trans.  Path.  Soc.  of  London,  1896,  xxi,  4;  Brit.  Med.  Journ., 

1896,  i,  1034. 


CHAPTER  XVIII 
PANCREATIC  CYSTS 

Although  cysts  of  the  pancreas  cannot  be  said  to  be  of 
frequent  occurrence,  they  have  to  be  taken  into  account 
in  the  diagnosis  of  any  cystic  tumour  in  the  abdomen ; 
for,  as  will  be  seen  later,  they  may  appear  in  various 
regions  and  may  simulate  many  other  diseases. 

A  search  through  the  literature  reveals  the  fact  that, 
excluding  thirteen  cases  in  our  own  experience,  one  hun- 
dred and  sixty  cases  of  operation  for  pancreatic  cysts 
have  been  recorded.  Although  larger  numbers  have  been 
reported  in  various  works,  the  above  figure  is  probably  as 
nearly  correct  as  possible;  for  on  verifying  the  records, 
the  same  case  had  sometimes  been  reported  twice,  and, 
in  many,  the  details  were  so  meagre  that  the  nature  of 
the  operation  was  not  even  given.  Dr.  Hale  White  has 
recorded  the  fact  that  in  nearly  six  thousand  post-mor- 
tem examinations  at  Guy's  Hospital  from  1883  to  1894, 
pancreatic  cysts  were  only  found  in  four  cases,  and  one 
of  these  was  a  hydatid  cyst. 

Cysts  of  the  pancreas  may  be  divided  into  false  and  true. 
The  false  or  pseudo-cysts  may  be  due  to  a  distension 
of  the  lesser  peritoneal  sac,  or  to  a  localised  collection  of 
fluid  in  the  neighbourhood  of  the  pancreas. 

Seeing  that  simple  drainage  is  usually  sufficient  to 
bring  about  relief  or  cure  of  the  disease,  surgery  offers  a 
poor  opportunity  for  pathological  intervention,  since 
experience  has  shown  that  the  patient's  interests  are  best 
considered  by  a  limitation  of  the  incision  to  a  size  suffi- 
cient to  empty  and  drain  the  cyst,  and  not  sufficiently 
large  to  satisfy  pathological  investigation;    hence  it  is 

487 


488       The  Pancreas:  Its  Surgery  and  Pathology 


highly  probable  that  many  reported  cases  of  operation  for 
pancreatic  cysts  have  been  for  cysts  of  other  organs,  and 
it  is  an  undoubted  fact  that  quite  a  number  of  the  cysts 
supposed  to  originate  from  the  pancreas  are  pseudo-cysts. 
True  cysts  may  be  due  to  retention  from  various  causes, 
to  parasitic  disease, — e.g.,  hydatids, — to  new-growths, 
as  in  proliferation  cysts,  and  to  haemorrhage.  A  few 
cases  of  congenital  cystic  disease  have  been  recorded. 

The  greater  number  of 
chronic  cases  that  come  un- 
der the  care  of  the  surgeon 
are  due  to  retention  of  the 
gland  secretion,  the  outflow 
of  which  is  hindered  in  some 
way. 

Senn  found  that  ligature  of 
the  pancreatic  duct  did  not 
result  in  the  formation  of  a 
cyst,  though  chronic  or  inter- 
mittent obstruction  might  re- 
sult in  cyst-formation ;  just  as 
ligature  of  a  ureter,  or  acute 
obstruction,  leads  to  atrophy 
of  the  kidney,  though  chronic 
obstruction  or  an  obstruction 
of  an  intermittent  character 
tends  to  the  development  of 
hydronephrosis. 
The  outflow  of  secretion  in  the  pancreas  may  be  hin- 
dered in  different  ways  by  obstruction  of  the  excretory 
duct,  or  by  a  combination  of  compression  from  without 
and  obstruction  from  within.  The  most  frequent  cause 
is  probably  chronic  interstitial  pancreatitis,  in  which 
compression  and  constriction  of  the  ducts  result  from  the 
development  and  contraction  of  connective  tissue,  thus 
leading  to  stagnation  of  the  secretion.     Wirsung's  duct 


Fig.  152. — Calcification  of 
the  orifice  of  the  duct  of  Wir- 
sung  and  dilatation  of  the  duct 
(Univ.    Coll.    Museum,    3196). 


Pancreatic  Cysts  489 

may  be  closed  by  gradual  compression,  as,  for  instance, 
in  the  development  of  a  tumour  along  its  course,  or  by 
the  gradual  development  of  a  duodenal  tumour,  or  a 
stricture  due  to  ulceration,  which  compresses  the  orifice 
of  the  duct.  Pressure  by  swollen  lymphatic  glands,  or  by 
adhesions  near  the  head  of  the  pancreas,  or  even  by  a 
gall-stone  or  Wirsung's  duct,  may  lead  to  stagnation  of 
secretion,  and  thus  to  cystic  development. 

Occasionally  a  cyst  of  the  pancreas  may  result  from 
chronic  pancreatitis  due  to  ulceration  extending  into  the 
pancreas  from  a  chronic  ulcer  of  the  posterior  wall  of  the 
stomach,  as  in  a  case  which  was  treated  successfully  by 
gastro-enterostomy,  and  at  the  same  time  drainage  of 
the  cyst,  by  one  of  us. 

Large  cysts  may  also  be  caused  by  obstruction  within 
the  duct,  as,  for  instance,  by  a  pancreatic  calculus  or  by 
a  gall-stone  in  the  ampulla  of  Vater. 

Doubtless  some  cysts  are  altogether  independent  of 
obstruction  and  cannot  be  accounted  for  by  any  of  these 
explanations. 

A  particularly  interesting  case  has  been  reported  by 
McPhedran,  in  which  a  pseudo-cyst  and  a  true  cyst  were 
observed  in  the  same  individual : 

"  G.  A.  B.,  male,  aged  fifty-three,  in  1891  had  an  attack 
of  biliary  colic,  with  well-marked  jaundice  and  pale 
motions.  Had  two  or  three  similar  attacks  every  year. 
Condition  became  gradually  worse  and  there  was  almost 
constantly  some  epigastric  discomfort,  indigestion,  and 
flatulence.  One  severe  attack  of  pain  lasted  three  days. 
The  epigastrium  was  tender  and  pain  radiated  in  several 
directions.  Was  losing  flesh.  On  examination  there  was 
a  thickening  to  be  felt  on  deep  pressure  in  the  epigastrium. 
Three  days  later  a  large,  smooth,  cyst-like  tumour  was 
found  in  the  epigastrium,  extending  from  the  right  para- 
sternal line  to  the  left  mammary  line  and  down  to  the 
umbilicus.  The  upper  boundary  was  ill  defined.  The 
stomach  resonance  was  above  and  to  the  left.     A  C5^stic 


490       The  Pancreas:  Its  Surgery  and  Pathology 

collection  in  the  bursa  omentalis  was  diagnosed,  and  the 
abdomen  opened.  The  cyst  was  emptied.  At  the  bot- 
tom lay  the  pancreas,  irregularly  enlarged  and  firm,  but 
somewhat  elastic.  The  peritoneum  over  it  was  smooth 
and  healthy  looking.  There  was  no  sign  of  hemorrhage 
anywhere.  Five  months  later  a  tumour  was  again  found 
in  the  epigastrium.  It  extended  down  to  the  level  of  the 
anterior  superior  spinous  process,  and  laterally  to  the 
mammary  line  on  the  right,  and  the  anterior  axillary  line 
on  the  left.  It  forced  the  diaphragm  upwards,  so  that 
the  cardiac  impulse  was  in  the  fourth  intercostal  space. 
The  abdomen  was  again  opened  and  a  cyst  exposed 
lying  behind  the  stomach.  The  cyst  wall  was  about  2 
mm.  thick.  The  fluid  was  opaque,  whitish,  and  contained 
many  flocculi  and  masses  of  fibrin.  It  was  alkaline  in 
reaction,  and  contained  albumin,  but  no  digestive  ferment. 
After  drainage  the  cavity  contracted  rapidly,  but  a  fistula 
persisted,  and  the  discharge  from  this  irritated  the  skin. 
On  examination  it  was  found  to  possess  marked  action  on 
albuminoids,  fats,  and  starches,  leaving  no  doubt  as  to  the 
presence  of  pancreatic  secretion.  The  condition  causing 
the  repeated  attacks  of  colic  lay  in  the  pancreas,  and  may 
have  been  a  calculus  or  a  localised  inflammatory  deposit 
causing  mechanical  obstruction.  In  the  most  acute 
attacks  the  symptoms  were  those  of  acute  pancreatitis." 

The  symptoms  produced  by  a  pancreatic  cyst  vary 
according  to  the  cause,  as  well  as  from  the  size  and  the 
seat  of  the  tumour.  They  are  at  first  dependent  on  the 
disease  which  leads  to  the  cystic  formation,  though  later 
the  pressure  exercised  by  the  tumour  itself  on  the  neigh- 
bouring viscera  has  to  be  taken  into  account.  Seeing 
that  cystic  disease  is  generally  associated  with  some  pan- 
creatitis, either  local  or  general,  we  may  expect  to  find 
digestive  disturbance  with  loss  of  fiesh  and  pain  at  the 
pit  of  the  stomach  quite  early  in  the  disease,  preceding  by 
some  time  the  recognition  of  the  cyst  at  the  surface.  If 
the  cause  be  dependent  on  some  obstruction  in  the  duct, 
we  may  expect  to  find  paroxysmal  pains  accompanied 
by  vomiting  and  followed  by  jaundice  and  wasting. 


Pancreatic  Cysts 


491 


If  the  interstitial  pancreatitis  is  at  all  extensive,  there 
will  be  marked  loss  of  flesh  associated  with  fatty  stools, 
azotorrhoea,  and  bulky,  pale  motions,  and  rarely  the 
presence  of  glucose  in  the  urine.  In  all  the  cases  of  pan- 
creatic cyst  that  we  have  recently  observed  there  has 
been  a  well-marked  pancreatic  reaction  in  the  urine, 
indicating  catarrh  of  the  pancreatic  ducts,  or  interstitial 
inflammation. 

The  Rontgen  rays  may  also  form  a  useful  help  in  diag- 


Fig.  153. — Diagram  to  show  the  relations  of  the  peritoneal  reflections 
of  the  pancreas  (Testut) . 


nosis  in  certain  cases,  as  they  may  establish  the  presence 
or  absence  of  pancreatic  calculi. 

It  is  to  be  borne  in  mind  that  there  have  been  cases 
of  pancreatic  cyst,  presenting  very  few  symptoms  except 
the  presence  of  a  tumour,  which  have  been  under  observa- 
tion for  a  long  time  and  have  needed  no  active  treatment, 
but  these  cases  are  exceptional.  On  the  other  hand,  the 
tumour  may  be  associated  with  severe  pain  and  distress 
and  with  marked  digestive  and  metabolic  symptoms. 


492       The  Pancreas:  Its  Surgery  and  Pathology 


t 


The  physical  signs  of  cysts  of  the  pancreas  are  by  no 
means  constant.  A  consideration  of  the  peritoneal  reflec- 
tions from  the  pancreas  on  to  the  viscera,  and  how  they 
influence  the  ultimate  position  and  relations  of  pancreatic 
cysts,  will  render  the  reason  for  this  clear  (Fig,  153).  For 
instance,  a  tumour  may  spring  from  ,the  anterior  surface 
of  the  head  or  body  of  the  pancreas  above  the  stomach, 

between  it  and  the  liver,  or, 
between  it  and  the  transverse 
mesocolon.     On  the  state  of 
"^'x""        N\^'     1     distension  of  the  stomach  will 
depend  the  extent  of  contact 
of  the  tumour  with   the  ab- 
dominal wall.     By  distending 
the  stomach  with  air  through 
a  tube,  or  by  giving  doses  of 
soda  and  tartaric  acid  in  sep- 
arate draughts,  the  relation  of 
the  stomach  to  the  cyst  can 
be  readily  shown.     If  a  cystic 
tumour   arise   from  the  pan- 
creas    to    the    right    of    the 
omental  bursal    reflection,   it 
may  make  its  way  forwards 
to  the  right   hypochondrium 
and  simulate  a  gall-bladder  or 
right  renal  or  suprarenal  cyst. 
Should  a  cyst  arise  from  the 
posterior  part  of  the  head  or  tail  of  the  gland,  it  may 
project  either  into  the  right  or  left  lumbar  region  and 
resemble  a  cyst  of  the  kidney.     If  a  tumour  springs  from 
the  head  of  the  pancreas  below  the  reflection  of  the 
transverse  mesocolon,  but  to  the  right  of  the  mesenteric 
vessels,  it  will  reach  the  surface  below  the  hepatic  flexure 
of  the  colon  on  the  right  side,  and  may  simulate  a  right 
renal  tumour,  or  a  tumour  of  the  caecum,  or  ascending 


Fig-  154- 

(Figs.  154  to  158  are  a  series 
of  diagrams  to  show  the  direc- 
tions in  which  pancreatic  cysts 
may  develop.) 


Fig.   i: 


Fig.  15  7- 


Fig.  156. 


493 


Fig.  is8. 


494       The  Pancreas:  Its  Surgery  and  Pathology 

colon,  as  the  mesentery  will  prevent  it  passing  to  the 
left  of  the  spine ;  but  should  it  arise  from  the  small  por- 
tion of  the  processus  uncinatus  on  the  left  of  the  mesenteric 
vessels,  but  below  the  attachment  of  the  transverse  meso- 
colon, it  may  burrow  between  the  layers  of  the  mesentery 
and  simulate  a  mesenteric  cyst,  or  it  may  bulge  on  the 
left  of  the  mesentery  and  reach  the  surface  below  the 
transverse  colon  on  the  left  of  the  spine,  when  it  may 
resemble  a  left  renal  or  ovarian  cyst,  or  a  tumour  of  the 
descending  colon,  or  small  intestine.  A  tumour  arising 
from  the  body  or  tail  of  the  pancreas  above  the  reflection 
of  the  transverse  mesocolon  will  pass  upwards  beneath 
the  left  costal  margin,  and  resemble  a  cyst  of  the  spleen, 
or  of  the  left  lobe  of  the  liver.  A  pancreatic  cyst  in  this 
region  may  be  opened  and  drained  under  the  idea  that 
it  is  a  cyst  of  the  spleen,  and  a  chronic  abscess  of  the  spleen 
may,  on  the  other  hand,  be  opened  and  drained  under 
the  idea  that  it  is  a  cyst  of  the  pancreas. 

Tumours  springing  from  the  pancreas  on  the  left  of  the 
duodeno-jejunal  junction,  where  the  lower  surface  of  the 
gland  lies  on  the  transverse  mesocolon,  have  a  tendency 
to  press  the  great  omentum  forward  and  to  project  above 
the  transverse  colon,  but  they  may  grow  downwards 
towards  the  central  region  of  the  abdomen  and  arch  the 
transverse  colon,  or  even  project  below  it,  so  that  the  colon 
lies  above  the  tumour.  The  relationship  of  the  colon  to 
the  cyst  may  be  ascertained  by  distending  the  colon  with 
air  introduced  per  anum.  In  an  interesting  case  recorded 
by  Dr.  S.  P.  Phillips  a  thin-walled  pancreatic  cyst  spring- 
ing from  the  head  of  the  pancreas  completely  filled  the 
abdomen  and  presented  the  physical  signs  of  ascites. 

The  explanation  of  these  variations,  which  may,  and 
often  do,  lead  to  difficulties  in  diagnosis,  is  an  anatomical 
one,  and  depends  on  the  site  of  origin  of  the  cyst,  which 
in  making  its  way  to  the  surface  proceeds  in  the  line  of 
least  resistance,  and  is  thus  influenced  by  the  reflections 


Pancreatic  Cysts  495 


Fig.  159. — a,  Traumatic  pancreatic  effusion  into  the  lesser  peritoneal 
sac,  in  a  boy  set.  two  years,  knocked  down  by  a  cab ;  b,  cyst  of  pancreas 
treated  by  incision  and  drainage,  man  set.  thirty-five  years;  well  seven 
years  later. 


Fig.  160. — a,  Cyst  of  tail  of  pancreas  treated  by  incision  and  drain- 
age ;  cure,  b,  Cyst  of  pancreas  from  man  set.  thirty-seven  years ;  drain- 
age, recovery. 


496       The  Pancreas:  Its  Surgery  and  Pathology 


Fig.  161. — a,  Pseudo-cyst  of  pancreas  formed  around  necrosed  pan- 
creas in  a  man  ast.  fifty-eight  years.  Patient  in  good  health  two  years 
later,  b,  Cyst  of  pancreas  treated  by  drainage;  man  set.  fifty-three 
years;  short  fistula  remains,  otherwise  well. 


Fig.  162. — a,  Cyst  of  body  of  pancreas;  drainage;   recovery,      b,  Pan- 
creatic cyst  resembling  ovarian  tumour. 


Pancreatic  Cysts 


497 


of  the  peritoneum  and  the  arrangement  of  the  viscera 
overlying  the  gland- 
Diagnosis. — A  cyst  of  the  pancreas  may  thus  simulate 
a  dilated  and  tense  gall-bladder,  a  cyst  of  the  liver,  spleen, 
or  kidney,  an  omental  or  mesenteric  cyst,  an  ovarian  or 
uterine  cyst,  a  cystic  dilatation  of  the  bile-duct,  a  supra- 
renal cyst,  a  tubercular  peritonitis,  or  even  an  ascites. 
It  is  evident,  therefore,  that  the  presence  of  a  cystic 
tumour  alone,  even  in  a  characteristic  position,  will  not 
justify  the  diagnosis  of  cyst  of 
the  pancreas,  though,  as  a  rule, 
the  combination  of  symptoms 
together  with  the  physical  signs 
should  leave  little  doubt  in  the 
majority  of  cases  as  to  the  na- 
ture of  a  tumour,  even  before  an 
exploration  of  the  abdomen  is 
done.  It  used  to  be  a  favourite 
diagnostic  method  to  explore  by 
a  hollow  needle  any  cystic  tu- 
mour ;  but  it  can  be  only  under 
very  exceptional  circumstances 
that  this  aid  to  diagnosis  would 
be  justifiable,  as  it  is  by  no 
means  devoid  of  danger  from 
perforation  of  an  overlying  vis- 
cus  {e.  g.,  stomach,  colon,  etc.), 
or  perforation  of  a  large  vessel 

or  extravasation  of  the  cyst  contents.  Not  only  so,  but 
the  examination  of  the  contents  will  not  always  make  the 
diagnosis  certain.  If,  however,  such  an  exploration  be 
decided  on,  it  is  better  to  employ  a  small  aspirator  needle, 
and  at  the  same  time  to  completely  empty  the  cyst, 
which,  if  tense,  would  otherwise  be  liable  to  leak  into  the 
peritoneal  cavity,  and  produce  disastrous  consequences. 
While  it  is  easy  to  say  what  will  be  the  physical  signs  on 
32 


Fig.  163. — Cyst  of  tail  of 
pancreas,  from  a  woman  set. 
thirty-eight  years ;  drain- 
age; recovery.  Recurrence; 
excision  of  cyst;    recovery. 


498       The  Pancreas:  Its  Surgery  and  Pathology 


percussion  and  palpation  of  a  cyst  appearing  above,  be- 
hind, or  below  the  stomach,  or  above,  behind,  or  below 
the  transverse  colon,  it  will  be  seen  that  no  one  descrip- 
tion can  in  any  way  guide  the  sur- 
geon as  to  the  regular  signs  to  be 
found  in  a  pancreatic  cyst  reaching 
the  surface. 

The  shape  of  a  cyst  varies  accord- 
ing to  the  way  in  which  it  originates 
from  Wirsung's  duct,  or  from  the 
smaller  canals  within  the  gland. 
Thus  there  may  be  a  rosary-like 
dilatation  of  the  whole  duct,  as  in 
a  photograph  taken  from  a  specimen 
in  the  College  of  Surgeons'  Museum, 
shown  in  the  illustration  (Fig.  164). 
Virchow  termed  this  "ranula  pan- 
creatica,"  from  its  analogy  to  the 
well-known  cystic  tumour  in  the 
mouth. 

If  .  several  small  ducts   are  con- 
stricted, the  resulting  cysts  may  be 
small  and  multiple,  especially  if  as- 
sociated with   diffuse  chronic  pan- 
creatitis (Fig.  165).     In  case  of  par- 
tial   cystic-dilatation   of   Wirsung's 
duct,  large  cysts  may  form  which 
may  be  oval  or  rounded  and  may 
vary  from  the  size  of  a  fist  to  enor- 
mous sacs  containing  as  much  as  20 
to    30    pints    of    fluid,    though   the 
ordinary  size  of  pancreatic  cysts  is 
something  between  that  of  an  orange  and  a  child's  head. 
The  thickness  of  the  cyst '  wall  will  vary  according  to 
the  amount  of  pancreatic  tissue  entering  into  its  struc- 
ture, but  in  some  cases  it  may  be  quite  thin.     It  should 


Fig.  164. — Dilata- 
tion of  the  duct  of  Wir- 
sung  (Royal  Coll.  of 
Surg.  Museum,  2832  A). 


Pancreatic  Cysts  499 

not  be  forgotten  that  large  blood-vessels  may  be  encoun- 


Fig.    165. — Pancreas   showing   small   retention   cysts    (Leeds   Medical 
School  Museum,  E  E  203). 

tered  in  the  walls  of  the  cyst.  The  lining  of  the  cyst  is  gen- 
erally smooth,  but  in  some 
cases  it  may  be  roughened 
and  show  ridges  and  septa 
the  remains  of  several  orig- 
inal cysts ;  or  there  may  be 
found,  adherent  to  the  inner 
surface  of  the  cyst,  clotted 
remains  of  profuse  hasmor- 
rhages.  The  contents  of  a 
cyst  may  resemble  water, 
and  may  give  the  appear- 
ance of  a  hydronephrosis 
having  been  tapped,  or  the 
fluid  may  be  thick  and 
slimy.  More  frequently, 
however,  the  contents  of 
the  cyst  are  light  brown, 
or  coffee-ground,  in  colour. 
The  fluid  may  also  be 
syrup-like  and  gelatinous, 
or  colloid  or  purulent.  In  some  cases  it  may  be  yellowish- 
green,  as  if  mixed  with  bile. 


Fig.  166. — Retention  cyst  of 
the  tail  of  the  pancreas  (St. 
George's  Hosp.  Museum,  202  A). 


500       The  Pancreas:  Its  Surgery  and  Pathology 

It  will  thus  be  seen  that  the  naked-eye  appearances  of 

the  contents  of  the  cyst  do  not  always  form  a  guide  as  to 

its  true  nature.     A  chemical  analysis  of  the  fluid  often 

affords  positive  assistance.     The  fluid  from  a  pancreatic 

cyst  is  alkaline  in  reaction,  and  generally  of  low  specific 

gravity,  i.oio  to  1.020,  although  Gussenbauer  in  one  case 

found  a  specific  gravity  of  1.160.     The  amount  of  solid 

matter  is  not  high ;  thus,  Herter  analysed  the  contents  of 

two  pancreatic  cysts  and  gives  the  following  results  of 

three  examinations : 

I  II  III 

Total  solids 24.1%  24.1%  23.8% 

Organic  matter i7-9%  i4-9%  18.5% 

.  Ash 6.2%  9.2%  8.7% 

Albumin  is  always  present,  and,  occasionally,  mucin  also. 
Traces  of  urea  have  been  noted  in  some  instances,  and  cho- 
lesterin  is  frequently  found.  A  very  complete  analysis 
of  the  contents  of  a  pancreatic  cyst  has  been  recorded  by 
Alay  and  Rispal.  In  their  case  the  following  results  were 
obtained :  Reaction  feebly  alkaline ,  albumin  8 . 9  grams  per 
mille (serum  albumin  5.2  grams  per  mille,  globulin  0.6  gram 
per  mille,  albumose  3.0  grams  per  mille,  peptone  nil),  urea 
0.14 gram  per  mille,  uric  acid  traces,  fat  and  cholesterin o.  1 6 
gram  per  mille,  sugar  nil,  acetone  about  0.05  gram  per  mille, 
chlorides  5.8  grams  per  mille,  phosphates  0.16  gram  per 
mille,  sulphate  traces,  calcium  and  magnesium  0.05  gram 
per  mille.     The  ash  contained  iron  and  traces  of  copper. 

Microscopically  blood  cells  are  usually  found.  There 
may  be  epithelial  cells,  fat  globules,  and  cholesterin  crys- 
tals. 

The  most  important  characteristic,  however,  is  the 
possession  by  the  fluid  of  digestive  powers  resembling 
those  of  pancreatic  juice.  When  it  is  found  to  readily 
digest  albumin,  starch,  and  fat,  there  can  be  no  doubt  as 
to  the  nature  of  the  cyst  from  which  it  is  derived,  but  the 
exact  value  of  the  discovery  of  one  or  other  of  the  fer- 
ments alone  is  still  a  matter  of  dispute.     Korte  considers 


Pancreatic  Cysts  501 

that  a  powerful  starch-converting  ferment  is  of  great 
diagnostic  value,  and  it  is  no  doubt  very  suggestive,  but 
it  must  be  remembered  that  von  Jaksch  has  shown  that 
the  fluid  from  various  abdominal  cysts,  and  even  from 
cases  of  ascites,  has  distinct  starch-converting  powers, 
so  that  it  is  now  generally  acknowledged  that  the  presence 
of  a  diastatic  ferment  alone  is  of  little  value  in  diagnosis. 
According  to  Boas,  the  presence  of  an  albumin-digesting 
ferment  is  most  characteristic,  but  in  many  cases  of  un- 
doubted pancreatic  cyst  this  has  been  absent,  especially 
in  old  encapsuled  cysts.  Its  absence  in  more  recently 
formed  cysts  is  explicable  by  the  fluid  not  having  been 
activated  by  the  enterokinase  of  the  succus  entericus, 
while  its  presence  in  other  cases  may  be  due  to  the  action 
of  soluble  calcium  salts,  etc.,  which,  according  to  Delez- 
enne  and  Wohlgemuth,  have  a  similar  effect  to  enteroki- 
nase. Since  the  fat-splitting  power  of  pancreatic  juice 
is  its  most  characteristic  property,  it  might  be  expected 
that  the  possession  of  this  power  by  a  fluid  will  at  once 
decide  its  origin,  and,  according  to  our  own  observ^ations 
and  those  of  Zeehuisen,  this  is,  in  fact,  the  case.  Unfor- 
tunately this  question  has  not  been  gone  into  in  many- 
cases,  but  as  the  methods  of  examination  now  available 
are  comparatively  simple,  it  is  to  be  hoped  that  a  larger 
body  of  evidence  will  shortly  be  available. 

With  regard  to  the  results  of  an  examination  for  fer- 
ments, it  may  be  said  that  the  presence  of  all  the  enzymes 
in  considerable  amounts  points  to  a  cyst  arising  from, 
or  directly  connected  with,  the  pancreas,  while  their  ab- 
sence is  of  no  value  one  way  or  the  other.  The  presence 
of  a  starch-converting  ferment  alone  is  of  little  value  in 
diagnosis,  but  the  proteolytic  and  fat-splitting  ferments 
are  important,  and  afford  presiimptive  evidence  of  a  cyst 
of  pancreatic  origin.  The  presence  of  the  ferments  does 
not  necessarily  mean  that  the  fluid  is  contained  in  a  true 
pancreatic  cyst,  however,  for  they  may  be  found  in  pseudo- 


502       The  Pancreas:  Its  Surgery  and  Pathology 

cysts  arising  from  injury  or  laceration  of  the  pancreas. 
In  such  cases  the  ferments  are  furnished  by  the  pancreatic 
secretion  finding  its  way  through  the  injured  or  torn  peri- 
toneum into  the  lesser  sac,  where  they  mingle  with  the 
inflammatory  exudate  forming  the  bulk  of  the  fluid.  The 
digestive  powers  of  a  fluid  of  this  description  are  not  so 
well  marked  as  those  seen  in  a  typical  pancreatic  cyst, 
but  they  may  be  equally  as  active  as  those  met  with  in 
true  cysts  of  some  standing,  in  which  the  surrounding 
pancreatic  substance  has  been  replaced  by  fibrous  tissue 
from  the  associated  inflammatory  changes. 

The  termination  of  pancreatic  cysts,  in  the  absence  of 
treatment,  varies  in  different  cases.  There  is  usually 
a  steady  progress  of  the  disease  that  has  caused  the  cystic 
condition — as,  for  instance,  in  the  case  of  interstitial 
pancreatitis  towards  atrophy,  and  its  consequence,  diabe- 
tes; but  pressure  symptoms  may  produce  danger  before 
this  slower  termination,  or  the  cyst  may  rupture  into  the 
peritoneal  cavity  and  cause  death  by  shock  or  by  perito- 
nitis. Rupture  into  the  stomach  or  intestine  has  also  been 
known  to  occur. 

In  some  cases  pancreatic  cysts  have  existed  for  many 
years  without  producing  any  serious  symptoms,  though 
this  is  exceptional. 

Treatment. — It  is  quite  clear  that  medical  treatment 
can  be  of  no  avail  in  the  case  of  pancreatic  cysts,  and  that 
surgical  treatment  alone  is  available  for  relief  or  cure. 

Aspiration  and  other  forms  of  tapping  are  inadequate 
and  ineffectual  methods,  which  are  attended  with  more 
danger  than  is  the  operation  of  incision  and  drainage. 
They  are,  therefore,  not  to  be  recommended,  even  for 
diagnostic  purposes.  Occasionally  complete  extirpation 
of  the  cyst. may  be  performed,  as  in  a  case  that  came  under 
the  care  of  one  of  us,  where  the  tumour  returned  a  few 
months  after  it  had  been  apparently  successfully  treated 
by  drainage;    but  the  greater  difficulty  in  performing 


Pancreatic  Cysts  503 

excision,  its  impracticability  in  certain  cases  and  the  greater 
mortality  attending  it,  as  compared  with  the  operation 
of  incision  and  drainage,  make  it  quite  clear  that  drainage 
should  always  have  a  fair  trial  unless  the  circumstances 
prove  to  be  very  exceptional,  as,  for  instance,  in  the  case 
of  a  cyst  of  the  tail  of  the  pancreas,  or  in  the  case  of  a 
pedunculated  cyst. 

As  to  the  situation  for  drainage,  that  will  depend  on 
circumstances.  The  tumour  will  usually  be  attacked 
most  readily  from  the  front  at  a  point  where  it  very  nearly 
reaches  the  surface.  Occasionally,  however,  it  may  be 
drained  from  the  loin. 

Fistula  does  not,  as  a  rule,  follow  the  drainage  of  pan- 
creatic cysts,  but  in  some  cases  a  small  fistula  may  persist 
and  may  go  on  for  years  without  hurt  to  the  patient  and 
with  very  little  discomfort. 

The  following  is  a  description  of  the  operation  usually 
performed:  An  incision  is  made  through  the  parietes 
opposite  the  most  prominent  part  of  the  cyst.  When 
the  peritoneum  is  opened,  the  finger  can  be  employed  to 
ascertain  the  relations  of  the  cyst  and  its  attachments. 
If  the  stomach  is  in  front  of  the  cyst,  it  will  be  better  to 
displace  that  viscus  upwards  and  to  make  a  slit  through 
the  great  omentum  in  order  to  expose  the  cyst  wall;  if 
the  colon  is  in  front,  it  may  be  displaced  downwards. 
But  no  rule  can  be  formulated,  as  the  cyst  must  be  reached 
in  the  most  convenient  way,  and  that  can  be  ascertained 
only  when  the  abdomen  is  open.  By  means  of  an  aspi- 
rator the  fluid  is  then  drawn  off,  and  an  opening  made  in 
the  cyst  sufficiently  large  to  allow  of  a  drainage-tube 
being  inserted.  The  tube  may  then  be  fixed  to  the  mar- 
gin of  the  incision  in  the  cyst  by  a  single  catgut  suture, 
and  if  the  opening  into  the  cyst  is  surrounded  by  a  purse- 
string  suture,  which  can  be  tightened  around  the  tube, 
all  fear  of  leakage  from  the  cyst  into  the  peritoneal  cavity 
is  avoided.     Any  vessels  coursing  over  the  cyst  must  be 


504      The  Pancreas:  Its  Surgery  and  Pathology 

avoided,  but  should  an  artery  or  vein  be  pricked,  it  must 
be  caught  between  pressure  forceps  and  ligatured. 

The  edge  of  the  cyst  may  then  be  fixed  to  the  aponeuro- 
sis by  three  or  four  sutures,  but  it  is  better  not  to  attach 
it  to  the  skin.  The  abdomen  is  then  closed,  and  if  the 
tube  is  sufficiently  long  it  will  readily  drain  into  a  bottle 
containing  some  antiseptic  fluid.  If,  on  exploration,  the 
cyst  is  found  to  have  a  narrow  attachment  to  the  pancreas 
and  the  adhesions  are  not  too  extensive,  it  may  possibly 
be  shelled  out,  or  the  pedicle  may  be  ligatured,  but  this 
is  rarely  feasible. 

Some  surgeons  have  suggested  the  desirability  of  fixing 
the  cyst  to  the  surface  and  only  opening  it  after  a  few 
days,  when  adhesions  have  formed,  but  this  operation 
h  deux  temps  seems  to  be  quite  unnecessary. 

Statistics.— In  the  cases  that  have  come  under  our 
personal  observation,  one  cyst  was  enucleated,  recovery 
following;  drainage  was  carried  out  in  ten  cases  of  true 
cyst,  recovery  following  in  nine ;  whereas  of  two  pseudo- 
cysts, one  due  to  traumatic  hsemorrhagic  pancreatitis  and 
the  other  to  necrotic  pancreatitis,  one  recovered. 

Of  the  one  hundred  and  sixty  cases  of  operation  re- 
corded by  others,  there  were  one  hundred  and  forty 
recoveries ;  in  four  cases  the  ultimate  issue  was  doubtful ; 
in  eight  out  of  the  one  hundred  and  forty  reported  re- 
coveries after  operation  the  patients  died  subsequently — 
one  from  diabetes  four  months  later,  one  from  hsemorrhage 
one-and-a-half  years  later,  one  from  concomitant  peri- 
tonitis seven  weeks  later,  one  from  a  zymotic  fever  a  few 
weeks  later,  and  three  from  causes  not  stated,  a  few  weeks 
later.  Death  is  recorded  as  the  result  of  operation  in 
twenty  cases.  In  five  of  these  the  cause  of  death  and 
the  time  after  operation  are  not  given.  One  patient  died 
in  collapse,  one  died  before  operation  could  be  completed 
(the  next  day),  one  died  from  "ileus,"  one  died  eighteen 
days  after  operation  (cause  not  stated),  two  died  from 


Pancreatic  Cysts  505 

shock,  one  died  from  gangrene  of  the  pancreas,  and  eight 
died  from  peritonitis ;  one  died  at  an  interval  not  stated, 
one  after  ninety-six  hours,  one  after  six  days,  one  after  an 
exploratory  incision,  two  after  two  days,  one  on  the 
eighth  day,  and  one  on  the  second  day.  In  one  hundred 
and  thirty-eight  cases  incision  and  drainage  were  per- 
formed, with  sixteen  deaths,  equal  to  a  mortality  of  11.6 
per  cent.  In  fifteen  excision  was  performed,  with  three 
deaths,  equal  to  a  mortality  of  20  per  cent.  In  seven 
partial  excision  was  done,  with  one  death,  equal  to  a  mor- 
tality of  14.3  per  cent. 

Although  larger  numbers  have  been  reported  by  others, 
the  above  figures  are  as  nearly  correct  as  possible,  for  on 
verifying  the  records  sometimes  the  same  case  had  been 
reported  twice,  in  others  wrong  dates  had  been  given,  and 
in  a  few  the  details  were  so  meagre  that  the  nature  of  the 
operation  was  not  given.  The  evidence  is  clearly  in 
favour  of  drainage,  but  the  mortality  should  certainly 
be  reduced  by  one-half. 

PROLIFERATION  CYSTS 

Many  of  these  tumours  are  on  the  border-line  between 
cystic  carcinoma  and  proliferating  cystomata,  and  it  is 
only  the  subsequent  course  of  events  that  indicates  to 
which  class  they  belong. 

The  cystic  epitheliomata,  or  carcinomata,  are  cystic 
formations,  generally  multilocular,  with  cancerous  depos- 
its in  their  walls.  There  are  usually  secondary  deposits 
of  growth  in  the  liver  or  adjoining  structures.  Only  very 
few  cases  have  been  reported,  and  the  presence  of  metas- 
tatic growths  generally  renders  them  inoperable. 

The  cystadenomata  or  cystic  simple  tumovirs,  although 
more  common  than  the  malignant  variety,  are  yet  uncom- 
mon. Cumston,  writing  in  the  "Annals  of  Surgery"  for 
February,  1903,  was  only  able  to  find  reports  of  fifteen 
cases.     They  are  almost  always  multilocular,  lined  with 


5o6       The  Pancreas:  Its  Surgery  and  Pathology 


cyHndrical  epithelium,  and  form  crypts,  or  polypoid 
masses,  projecting  into  the  cavity  of  the  cyst.  They  are 
more  common  in  the  tail  than  the  head  of  the  gland. 
Since  their  contents  are  frequently  blood-stained,  some 
observers  have  considered  that  they  are  of  hasmorrhagic 
origin  and  have  referred  to  them  as  "apoplectic  cysts." 

Others  believe  that 
they  are  formed  by 
the  fusion  of  min- 
ute cysts  resulting 
from  obstruction 
of  the  small  ex- 
cretory ducts  fol- 
lowing interstitial 
inflammation.  In 
support  of  this 
view  it  has  been 
pointed  out  that 
no  evidence  of  a 
proteolytic  fer- 
ment could  be 
found,  and  that  it 
was  possibly  used 
up  in  digesting  the 
walls  separating 
adjacent  cysts. 
The  proteolytic 
ferment  is  not, 
however,  always 
absent,  and  it  is 
sometimes  the  starch  or  fat-splitting  ferment  that  has 
been  lacking. 

A  case  in  which  a  multilocular  cystic  tumour  of  the 
pancreas  was  removed  with  good  results,  has  recently- 
been  reported  by  Mr.  J.  D.  Malcolm,  and  is  the  second  in 
which  this  surgeon  has  operated. 


Fig.   167. — Thin- walled  cyst  of  the  pancreas 
(Royal  Coll.  of  Surg.  Museum,  2834  A). 


Pancreatic  Cysts  507 

The  patient,  a  female,  aged  fifty,  felt  something  move 
in  her  abdomen  and  was  very  sick  about  six  months  before 
she  sought  medical  advice.  This  disturbance  soon  passed 
off  and  she  "forgot"  about  the  "lump,"  but  she  began 
to  lose  flesh  and  strength  about  that  time.  A  month 
before  she  fainted,  and  was  very  pale  for  the  following 
week.  The  faeces  were  "  like  ink"  for  three  days  and  then 
resumed  their  natural  colour.  Apparently  there  had 
been  a  hasmorrhage  into  the  upper  part  of  the  alimentary 


Fig.  168. — Multilocular  cystic  tumour  of  the  pancreas  (Royal  College 
of  Surgeons  Museum,  A  2835). 

tract.  The  patient  again  became  conscious  of  something 
abnormal  in  her  abdomen.  Her  general  condition  was 
good,  the  urine  was  normal,  and  the  bowels  acted  well 
without  medicine.  There  was  an  oval,  hard  tumour  in 
the  left  side  of  the  upper  abdomen  measuring  about  4 
inches  in  its  lateral  diameter  and  rather  more  from  above 
downwards.  It  had  considerable  mobility,  exactly  resem- 
bling that  of  a  large  loose  kidney,  the  greatest  fixity  being 
towards  the  spine.     The  percussion  note  over  the  most 


5o8       The  Pancreas:  Its  Surgery  and  Pathology 

prominent  parts  was  dull  before  and  behind,  the  area  of 
dulness  varying  with  the  position  of  the  tumour.  The 
right  kidney  was  somewhat  mobile.  A  malignant  growth 
in  a  loose  left  kidney,  the  capsule  of  which  had  not  yet 
ruptured,  was  diagnosed. 

At  the  Samaritan  Free  Hospital,  on  April  26,  1905, 
the  abdominal  cavity  was  opened  by  an  incision  outside 
the  left  rectus  muscle.  The  transverse  colon  was  seen 
to  be  displaced  downwards  and  pressed  forwards  by  a 
growth  between  it  and  the  stomach.  There  was  only  one 
layer  of  serous  membrane  over  the  tumour,  which  appar- 
ently had  developed  to  the  left  of  the  lesser  sac  of  the 
peritoneum.  The  kidney  was  in  normal  position  behind 
the  neoplasm  and  the  tail  of  the  pancreas  lay  across  the 
upper  inch,  or  rather  more,  of  its  anterior  surface,  inti- 
mately attached  to  it .  Many  vessels  over  the  tumour  were 
ligatured  as  they  were  divided,  and  the  mass  was  gradu- 
ally freed  without  much  loss  of  blood  until  its  only  attach- 
ment was  to  the  pancreas.  This  gland  was  cut  into 
so  as  to  get  the  whole  growth  away.  The  pancreatic 
tissue  bled  freely,  but  it  showed  no  friability,  and  liga- 
tures applied  to  it  held  well.  A  large  vein,  quite  a  third 
of  an  inch  in  diameter,  was  cut  across  and  there  was  a 
profuse  hcemorrhage  for  a  moment,  but  both  ends  were 
secured  with  forceps  and  safely  tied.  When  the  pancreas 
was  released  it  immediately  turned  round  so  that  its 
anterior  aspect  presented  unharmed.  Evidently  the 
new-growth  had  arisen  from  the  posterior  surface  of  the 
gland,  and  rather  from  the  upper  part  of  it.  The  fact 
that  the  pancreas  had  been  incised  gave  rise  to  no  sub- 
sequent trouble.  In  enucleating  the  tumour  both  layers 
of  the  transverse  mesocolon  were  divided  and  the  edges 
of  the  inferior  layer  were  brought  together  by  sutures. 
A  drainage-tube  was  inserted  through  an  incision  below 
the  twelfth  rib,  the  anterior  abdominal  wound  was  closed, 
and  healing  gave  no  trouble. 

From  the  first  there  was  considerable  distress  caused 
by  vomiting  and  retention  of  flatus.  The  bowels  acted 
when  enemata  were  given,  but  every  attempt  to  give  the 
patient  a  sufficient  quantity  of  food  was  followed  by 
symptoms  of  a  partial  obstruction  of  the  bowel,  and  there 
was  an  increasing  tendency  to  intestinal  distension.     A 


Pancreatic  Cysts  509 

great  deal  of  peristaltic  movement  became  visible  in  the 
epigastric  and  umbilical  regions  and  down  almost  to  the 
pubes.  It  was  thought  that  the  small  intestine  was  adher- 
ent somewhere,  probably  to  the  wound  of  the  transverse 
mesocolon,  and  as  the  patient  was  losing  ground  the  abdo- 
men was  reopened  on  the  sixteenth  day  after  the  operation. 
It  was  then  obvious  that  the  large  intestine  was  at  fault 
and  that  the  difficulty  was  caused  by  an  unusually  acute 
angle  at  the  splenic  flexure,  the  mobility  of  the  transverse 
colon  being  interfered  with  by  adhesions  between  it  and 
the  anterior  abdominal  wall.  The  ascending  and  trans- 
verse colons  were  elongated,  distended,  and  tortuous,  so 
as  to  fill  the  area  where  peristalsis  had  been  visible. 
The  adhesions  were  released,  a  lateral  anastomosis  was 
made  between  the  transverse  and  descending  colons, 
and  flatus  escaped  freely  from  the  rectum  a  few  hours 
after  the  operation.  There  was  for  a  time  a  tendency 
for  fasces  to  collect  in  the  colon,  but  there  were  no  further 
urgent  symptoms,  and  the  patient,  who  had  become  very 
emaciated,  gradually  put  on  flesh  and  left  the  hospital 
on  July  3.  She  was  seen  again  on  March  13,  1906,  when 
her  general  health  was  good  and  the  bowels  were  acting 
regularly  without  medicine.  She  complained  of  a  drag- 
ging pain  in  the  right  side,  and  the  left  kidney  was  much 
more  mobile  than  it  had  been,  but  a  belt  and  pad  gave 
relief. 

The  tumour  was  a  multilocular  cystoma  measuring 
about  4  inches  by  about  3I-  inches,  with  a  small  amount 
of  solid  tissue  here  and  there  between  the  cysts.  It  is 
preserved  in  the  museum  of  the  Royal  College  of  Sur- 
geons of  England. 

Congenital  cystic  disease  of  the  pancreas  is  exceedingly 
rare.  In  a  work  on  the  pancreas  by  Mayo  Robson  and 
Moynihan  reference  is  made  to  three  cases,  and  we  have 
been  unable  to  meet  with  a  record  of  any  other  instance 
subsequent  to  these.  The  condition  resembles  that  met 
with  in  other  organs,  with  which  it  has  been  associated 
in  at  least  one  case. 

Hosmorrhagic  Cysts. — Many  pancreatic  cysts  contain 
a  considerable  quantity  of  blood,  and  it  has  been  sought 


5IO       The  Pancreas:  Its  Surgery  and  Pathology 

to  distinguish  between  "hasmatomata,"  or  retention  cysts 
into  which  blood  has  escaped,  and  "apoplectic  cysts," 
resulting  from  haemorrhage  into  softened  gland  substance. 
Although  it  is  not  impossible  that  a  blood-containing  cyst 
may  arise  in  either  way,  there  is  no  certain  criterion  by 
which  they  can  be  distinguished,  and  even  if  it  were  possi- 
ble, the  distinction  would  merely  be  of  theoretical  inter- 
est and  of  no  practical  value.  The  arguments  bearing 
on  the  question  have  already  been  discussed  in  the  chap- 
ter on  pathology. 

Hydatid  cysts  of  the  pancreas  are  extremely  rare,  and 
present  no  surgical  peculiarities  calling  for  special  men- 
tion. They  must  be  treated  by  drainage  and  evacuation 
of  the  daughter  cysts,  and  on  no  account  must  incision  of 
the  cyst  be  attempted,  though  in  some  cases  it  may  be 
possible  to  completely  evacuate  the  endo-cyst  and  thus 
to  expedite  recovery. 

Literature 

Becourt:    " Recherches  sur  le  Pancreas,"  Strasb.,  1850. 

Boas:   "Magenkrankheiten,"  i,  295. 

Bozenaum  and  Ganignes:   Med.  Record,  1882. 

Brackel:   Zeit.  f.  Chir.,  xlix,  293. 

Bull:  New  York  Med.  Journ.,  1887. 

Cartledge:   Journ.  of  Amer.  Gynecol.,  Jan.,  1903,  p.  16. 

Churton:    Brit.  Med.  Journ.,  1894,  i,  1190;    Lancet,  1894,  i,  1374. 

Glutton:   St.  Thomas's  Hosp.  Rep.,  xxi. 

Cruveilhier:    "Traite  d'anftt.,"  1856,  iii,  366. 

Cumston:    Annals  of  Surg.,  Feb.,  1903,  p.  230;     Rev.  de  Chir.,  June, 

1903. 
Delezenne:   Brit.  Med.  Journ.,  Dec.  22,  1906,  p.  1785. 
Dieckhoff:   "Beitrage  z.  path.  Anat.  des  Pank.,"  Leipzig,  1896. 
Dixon:   Med.  Record,  March,  1884. 
Dunning:    Amer.  Journ.  of  Obstetr.,  1905,  p.  loi. 
Duponchel:    Med.  Rep.,  xxii,  162. 

Durante:   Cong,  d'ital  Chir.,  1893;   Ref.  Med.,  1893,  i'^>  359- 
Engel:    Med.  Jahrbuch  d.  ostern  Staates,   1840,  S.  411;     Ibid.,   1841, 

S.  193. 
Fisher:  Guy's  Hosp.  Rep.,  xxxiv. 
Fitz:  Amer.  Journ.  of  Med.  Sci.,  cxx,  184. 
Gilbert:    "Etudes  sur  les  Malades  du  Foie." 
Gourand:    Gaz.  de  Hopit.  Civils  et  Milit.,  April  2,  1904. 
Graham:   "Hydatid  Dis.  in  its  Clinical  Aspects,"  1891. 
Gussenbauer:   Langenbeck's  Arch.  f.  Chir.,  1883,  p.  355. 
Hagen:   Arch.  f.  klin.  Chir.,  Ixii. 
Hagenbech:   Deutsche  Zeitschr.  f.  Chir.,  1887,  xxvii,  no. 


Pancreatic  Cysts  511 

Hartmann:   Cong.  Franc,  de  Chir.,  1891;    Rev.  de  Gynecol,  et  de  Chir. 

Abdom.,  Sept.,  Oct.,  1905. 
Haynes:  Annals  of  Surg.,  1905,  xli,  950. 
Heaton:   Brit.  Med.  Journ.,  1901,  ii. 
Herter:   "Lectures  on  Chemical  Pathology." 
Hollander:   Med.  Press.,  Aug.  2,  1905,  p.  113. 
Hoppe:   Virchow's  Arch.,  1857,  xi,  96. 
Horrocks  and  Morton:   Lancet,  1897,  ^• 
V.  Jaksch:    Prager  med.  Wochenschr.,  1880,  S.  193 
Kellock:    Brit.  Med.  Journ.,  Dec.  16,  1905. 
Klob:   Oestern  Zeitschr.  f.  Heilk.,  i860,  529. 
Korte:   Berlin  Klinik,  Dec,  1896. 
Kiihnast:   Inaug.  Dissert.,  Breslau,  1887. 
Lloyd,  Jordan:   Brit,  Med.  Journ.,  Nov.,  1892. 
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Lynn:   Lancet,  1894. 

Malcolm:   Lancet,  June  16,  1906;   Tr.  Med.  Soc.  of  London,  xxi,  97. 
Marseron:   Thesis,  Paris,  1881. 
Martin:  Virchow's  Arch.,  1890. 
McPhedron:   Brit.  Med.  Journ.,  1897,  i-  1400. 
McReynolds:   Annals  of  Surg.,  1905,  xlii,  130. 
Manprofit:  Gaz.  m6d  de  Paris,  March  12,  1904. 
Murray:  Amer.  Med.,  July,  26,  1902,  133. 
Narath:   Arch.  f.  Chir.,  1,  4. 
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Park,  Roswell:   Amer.  Med.,  1903,  v,  949. 
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Zukowski:   Wien.  med.  Presse,  188 1. 


CHAPTER  XIX 
NEOPLASMS 

Tumours  of  the  pancreas  are  far  from  common  and  are 
usually  of  a  malignant  nature.  Among  the  lower  ani- 
mals, according  to  Nocard  and  Friedberger,  new-growths 
of  the  gland  are  especially  common  in  dogs  and  are  usually 
of  a  carcinomatous  or  adenomatous  type. 

Carcinoma. — Carcinoma  is  no  doubt  the  most  common 
of  the  neoplasms  found  in  the  pancreas,  but  until  recently 
it  has  not  figured  prominently  in  the  text-books,  the 
reason  probably  being,  as  Dr.  Sidney  Phillips  has  pointed 
out,  that  the  secondary  nodules  which  form  in  the  liver 
during  the  course  of  most  cases  of  cancer  of  the  pancreas 
are  so  much  more  readily  recognisable  both  during  life 
and  at  post-mortem  examination  than  a  nodule  of  cancer 
in  the  pancreas,  which  requires  to  be  searched  for,  that 
many  cases  of  cancer  of  the  pancreas  have  been  considered 
as  examples  of  cancer  of  the  livpr.  This  is  borne  out  by 
the  fact  that  since  more  attention  has  been  directed  to 
diseases  of  the  pancreas,  the  deaths  certified  from  cancer 
of  the  organ  have  risen,  while  the  deaths  certified  as 
from  cancer  of  the  liver  have  fallen  in  number.  Thus 
the  deaths  certified  to  the  Registrar-General  from  cancer 
of  the  pancreas  increased  year  by  year  from  281  in  1899 
to  436  in  1904,  the  most  marked  rise  being  from  340  in 
1903  to  436  in  1904,  while  in  the  same  twelve  months 
the  deaths  registered  from  cancer  of  the  liver  and  bile- 
ducts  fell  from  3901  to  3736.  No  doubt  many  cases  of 
cancer  of  the  pancreas  still  escape  registration  as  such. 

Out  of  53,000  necropsies  gathered  from  various  sources, 
where  post-mortem  examinations  were  presumably  care- 

512 


Neoplasms  513 

fully  made,  there  were  226  cases  of  primary  malignant 
disease  of  the  pancreas  (Roswell  Park),  but  as  these  in- 
clude Remo  Segre's  cases  from  the  Ospedale  Maggiore, 
Milan,  in  which  the  primary  and  secondary  growths  are 
not  separated,  the  proportion  of  primary  growths  is 
probably  not  so  large.  Secondary  growths  are  much 
more  common;  for  instance,  in  Eppinger's  statistics,  of 
13 14  necropsies  there  were  308  cancers  in  various  organs, 
of  which  19  were  in  the  pancreas,  but  of  these  only  2 
were  primary.  It  seems  adidsable  to  remark  here  that 
all  past  post-mortem 
records  with  regard  to  ,  .■'->:.'* 'V 7'' '^a 

cancer  of  the  pancreas  -,-  ■^^v^'Hllv''^ 

must   be   fallacious,   as  "         -*       --    ■  ..^w^ 

until  the  appearance  of  -'■'■■  '■'■''■  "'"'^ 

our   paper    on    chronic 
pancreatitis     in     July,        .h^,  . 
1900,   cases   of  chronic       "■^-' 
interstitial   pancreatitis 

causing  occlusion  of  the  -  ' 

common  bile-duct  were 
not  differentiated.  ,, 

The  tumour  in  cancer 

mav  takp  the-  fnrm  nf  ^^^-  169.— Primary  columnar-celled 
may    laKe    me    lorm    Ot  carcinoma  of  the  pancreas  (X  50). 

scirrhus  or  encephaloid 

cancer,  columnar  celled  carcinoma,  or  colloid  cancer,  and 
these  are  given  in  their  order  of  frequency.  Secondary 
deposits  may  be  found  in  any  situation,  but  are  most 
common  in  the  liver.  In  Fig.  170  is  shown  a  metastatic 
deposit  in  the  liver  secondary  to  cancer  of  the  pancreas, 
showing  how  the  secondary  disease  conforms  to  the  type 
of  the  primary. 

Cancer  usually  occurs  after  forty  years  of  age,  though 
we  have  met  with  a  case  of  cancer  of  the  head  of  the  pan- 
creas at  thirty-two  years  of  age,  and  rarely  it  has  been 
known  to  occur  in  childhood. 
33 


514       The  Pancreas:  Its  Surgery  and  Pathology 

Symptoms. — The  first  symptoms  are  loss  of  weight 
and  strength  with  indigestion  and  general  malaise,  pain 
being  usually  absent  or  unimportant.  When  the  head 
of  the  pancreas  is  involved  jaundice  rapidly  ensues,  the 
skin  assumes  a  dark  almost  black  colour,  unlike  the 
yellow  colour  of  jaundice  from  gall-stones,  the  liver 
swells,  and  the  gall-bladder  dilates.  The  patient  then 
seems  almost  to  dissolve  away,  the  loss  of  flesh  being  so 
rapid.  The  motions  become  pale  and  contain  fat  and 
muscle   fibre,   if  meat  be  taken.     Chemical   analysis   of 


Fig.  170. — a,  Primary  spheroidal-celled  carcinoma  of  the  pancreas; 
b,  edge  of  a  metastatic  deposit  in  the  liver,  from  the  same  case,  growth 
to  the  right,  liver  to  the  left  ( X  42). 


the  stools  shows  that  there  is  not  only  a  large  excess  of 
unabsorbed  fat,  but  that  the  "neutral  fat"  is  much  in- 
creased relative  to  the  "combined  fatty  acid,"  owing  to 
the  absence  of  the  fat-splitting  ferment  of  the  pancreatic 
juice  from  the  intestine.  In  cancer  of  the  head  of  the 
pancreas  obstruction  of  the  common  bile-duct  is,  as  a 
rule,  absolute  at  an  early  stage,  and  consequently  the 
fasces  contain  no  stercobilin.  The  urine  gives  no  "pan- 
creatic" reaction  by  the  improved  or  "  C-method"  in  most 
cases,  but  in  some  the  attendant  inflammatory  changes 
cause  a  more  or  less  marked  deposit  of  crystals.     By  the 


Neoplasms  515 

original  "A-reaction"  large,  slowly  soluble  crystals  may 
be  secured  in  most  instances,  but  in  some  no  reaction  is 
obtained,  and  in  others  it  may  be  necessary  to  examine 
several  specimens  of  urine,  and  to  make  more  than  one 
preparation  from  each,  before  they  can  be  obtained. 
In  interpreting  the  results  of  the  "pancreatic"  reaction 
in  the  urine  it  is  important  that  these  points  should  be 
borne  in  mind,  and  particularly  that  by  the  C-reaction  a 
deposit  of  crystals  due  to  a  pancreatitis,  associated  with 
the  spread  of  the  growth,  may  be  present  in  some  25  per 
cent,  of  cases  (see  table,  page  225),  or  otherwise  they  may 
lead  to  an  error  in  diagnosis.  Sugar  is  found  in  the  urine 
only  when  the  whole  gland  is  involved  in  the  growth,  or 
when  by  secondary  interstitial  pancreatitis  both  the 
secreting  parenchyma  and  the  islands  of  Langerhans 
have  been  destroyed.  It  is  therefore  not  commonly  met 
with. 

There  is,  as  a  rule,  no  difficulty  in  diagnosing  cancer  of 
the  head  of  the  pancreas  from  chronic  interstitial  pan- 
creatitis, for,  apart  from  the  usual  difference  in  the  re- 
sults of  the  pancreatic  reaction,  the  general  symptoms, 
especially  the  duration  and  mode  of  onset  of  the  disease, 
as  well  as  the  information  obtained  by  a  complete  and 
thorough  chemical  and  microscopical  examination  of  the 
faeces,  will  usually  enable  the  diagnosis  to  be  made.  In 
exceptional  cases,  especially  when  the  tumour  is  large 
and  growing  rapidly,  pain  may  be  severe  and  excruciating, 
and,  if  the  stomach  is  involved,  vomiting  assumes  a  prom- 
inent place.  In  some  instances  an  analysis  of  a  test 
meal  for  free  and  physiologically  active  hydrochloric 
acid  may  afford  useful  confirmatory  evidence  in  suspected 
cases  of  cancer,  but  although  their  absence  may  be  taken 
as  supporting  a  diagnosis  based  upon  other  grounds,  their 
presence,  even  in  considerable  amounts,  cannot  be  de- 
pended upon  as  indicating  the  simple  nature  of  a  tumour. 
The  haemorrhagic  tendency  in  connection  with  cancer  of 


5i6       The  Pancreas:  Its  Surgery  and  Pathology 

the  head  of  the  pancreas  and  jaundice  is  well  known,  but 
even  in  cancer  of  the  body  or  tail  of  the  organ  a  hsemor- 
rhagic  condition  may  ensue.  Probably  the  excretion  of 
lime  salts  from  the  blood  may  account  for  the  hsemorrhagic 
condition  and  for  the  relief  that  can  be  given  by  the  use 
of  calcium  chloride.  Bleeding  from  the  stomach  or  from 
the  nose  and  mouth,  and  from  the  intestine,  or  haemor- 
rhages under  the  skin  are  apt  to  occur  spontaneously, 
and  to  become  serious,  or  even  fatal,  and  in  case  of  opera- 
tion, unless  the  blood  be  previously  charged  with  lime 
salts,  bleeding  is  likely  to  occur  in  the  shape  of  persistent 
oozing,  both  at  the  time  of  operating  and  subsequently. 
When  the  tumour  attains  any  size,  it  may  be  palpated 
from  the  front,  but  in  ordinary  scirrhus  of  the  head  of 
the  pancreas  no  tumour  can  be  felt,  except  enlargement 
of  the  gall-bladder,  which  is  generally  present.  Occasion- 
ally, however,  there  may  be  no  marked  enlargement  of 
the  gall-bladder  until  late  in  the  case,  either  from  the 
cystic  or  hepatic  duct  being  gripped  by  the  growth,  or 
no  enlargement  throughout,  from  absence  of  the  viscus, 
as  in  the  case  reported  by  Stewart,  or  its  almost  complete 
obliteration  from  previous  inflammatory  changes.  Bronz- 
ing of  the  skin  may  come  on  if  the  adrenals  are  involved. 
Ascites  or  dropsy  of  the  lower  limbs  may  follow  from 
pressure  on  the  portal  vein  or  inferior  vena  cava,  or  from 
secondary  involvement  of  the  liver,  but  apart  from  pres- 
sure, slight  oedema  of  the  feet  is  often  an  early  sign. 
Death  occurs  from  exhaustion,  as  a  rule,  within  a  few 
months,  and  is  never  very  long  delayed;  in  fact,  cancer 
affecting  the  head  of  the  pancreas  is  more  rapidly  fatal 
than  when  occurring  in  any  other  organ.  The  typical 
clinical  picture  of  malignant  disease  of  the  pancreas  may 
thus  be  drawn:  A  patient  suffers  for  a  time  from  indef- 
inite symptoms  of  digestive  disturbance,  then  jaundice 
appears,  coming  gradually,  but  persistently  increasing; 
the  gall-bladder  is  usually  distended  and  the  liver  is  normal 


Neoplasms  517 

or  slightly  enlarged  at  first  and  greatly  enlarged  later. 
A  tumour  may  be  found  in  the  neighbourhood  of  the 
pancreas.  Cachexia  rapidly  develops,  and,  in  some  rare 
cases,  pain  disturbs  the  patient's  rest.  There  is  soon  a 
feeling  of  intense  prostration  and  weakness.  The  faeces 
are  massive  and  contain  fat,  the  normal  relation  between 
the; 'neutral  fat"  and  "combined  fatty  acids"  is  disturbed, 
and  an  undue  proportion  of  undigested  muscle  fibre  is 


Fig.  171. — Carcinoma  of  the  head  of  the  pancreas  causing  dilata- 
tion of  the  pancreatic  duct,  common  bile-duct,  and  gall-bladder  (St. 
Thomas'  Hosp.  Museum,  1414). 

present  in  the  stools.  The  urine  contains  albumin  fre- 
quently, and  sugar  and  fat  rarely.  The  whole  clinical 
course  is  run,  as  a  rule,  within  twelve  months,  and  after 
the  appearance  of  jaundice  within  from  six  to  eight  months. 
Differential  Diagnosis. — In  malignant  disease  of  the 
pancreas  the  symptoms  are  not  constant.  The  cases 
may  be  divided  into  three  chief  types:  (i)  Where  the 
t-umour  extends  to  the  right  and  compresses  or  occludes 
the   common  bile-duct   and  the   pancreatic   ducts.     (2) 


5i8       The  Pancreas:  Its  Surgery  and  Pathology 

Where  it  takes  an  upward  and  forward  direction  and, 
besides  compressing  the  bile-duct,  leads  to  pyloric  steno- 
sis. In  this  case,  to  the  typical  symptoms  are  added  those 
of  dilated  stomach.  (3)  Where  the  extension  is  back- 
wards, causing  compression  of  the  vena  cava,  and  of  the 
portal  veins,  thus  leading  to  an  early  onset  of  ascites  and 
later  to  oedema  of  the  lower  extremities.  When  the 
body  and  tail  of  the  pancreas  are  involved  the  symptoms 
are  atypical,  and  the  development  of  a  tumour  with  steady 
loss  of  strength  and  increasing  anasmia  are  such  as  might 
be  due  to  any  malignant  tumour  outside  the  pancreas. 
In  the  differential  diagnosis  of  cancer  of  the  head  of  the 
pancreas  we  must  consider  common-duct  cholelithiasis, 
interstitial  pancreatitis,  cancer  of  the  common  bile-duct, 
cancer  of  the  liver,  cancer  of  the  pylorus,  and  chronic 
catarrh  of  the  bile-ducts.  Whenever,  in  a  patient  at  or 
past  middle  age,  jaundice  comes  on  painlessly  and  becomes 
absolute,  at  the  same  time  that  the  gall-bladder  gradually 
enlarges  so  as  to  form  a  perceptible  tumour,  and  the  pa- 
tient rapidly  loses  flesh  and  strength,  a  diagnosis  of  cancer 
of  the  head  of  the  pancreas  will  probably  be  correct.  The 
diagnosis  will  be  made  more  certain  if  there  is  an  absence 
of  tenderness  below  the  right  costal  margin,  associated 
with  a  tumour  opposite  to,  or  above,  the  umbilicus,  hav- 
ing communicated  pulsation  and  not  moving  with  respira- 
tion. On  distending  the  stomach  with  air  or  carbonic 
acid  gas  it  will  be  found  that  the  tumour,  at  the  best 
rather  indefinite,  becomes  hidden  behind  the  resonant 
stomach,  and  that  the  distended  gall-bladder  becomes 
pushed  to  the  right.  If  cholelithiasis  has  preceded  the 
onset  of  cancer,  the  gall-bladder  will  not  be  enlarged, 
but  the  rapid  deterioration  of  health  and  the  presence  of 
anasarca  and  ascites  will,  as  a  rule,  leave  no  doubt  of  the 
nature  of  the  disease. 

In  common-duct  cholelithiasis  there  is  always  a  pre- 
liminary history  of  gall-stone   attacks,   though   it  may 


Neoplasms  5ig 

have  been  years  x^reviously.  The  jaundice  will  have  come 
on  after  pain  and  is  probably  never  absolute,  for  some 
bile  nearly  always  escapes  past  gall-stones  in  the  common 
duct.  The  bile  soon  becomes  infected,  and  ague -like 
seizures  follow,  with  an  irregular  temperature,  at  times 
almost  resembling  pyasmia.  In  place  of  a  distended  gall- 
bladder a  rigid  right  rectus  will  be  felt,  which  often  makes 
it  difficult  to  examine  the  parts  beneath.  A  tender  spot 
will  usually  be  found  an  inch  above,  and  to  the  right  of, 
the  umbilicus,  and  the  pain  will  be  found  to  pass  back- 
wards to  the  midscapular  region  or  to  a  spot  beneath 
the  right  shoulder-blade.  Whereas  cancer  of  the  head 
of  the  pancreas  is  only  a  question  of  months,  in  cholelithi- 
asis it  may  be  one  of  years. 

Pancreatic  catarrh  or  chronic  pancreatitis  frequently 
accompanies  gall-stones  in  the  common  duct  and  clears  up 
after  their  removal,  but  it  may  persist  after  the  cause  has 
passed  away.  Whenever  a  tumour  of  the  head  of  the 
pancreas  is  felt  during  a  gall-stone  operation,  especially 
if  before  middle  life,  hope  may  always  be  felt  that  the 
disease  may  be  simple  and  may  clear  up  by  the  drainage 
of  the  ducts.  A  long  history  is  in  favour  of  the  simple 
disease,  as  are  the  presence  of  adhesions,  the  history  of 
painful  attacks,  and  the  presence  of  tenderness  above  the 
umbilicus.  In  chronic  pancreatitis  it  is  not  uncommon 
to  find  enlarged  glands  in  the  free  border  of  the  lesser 
omentum,  but  they  are  discrete  when  the  disease  is  simple 
and  generally  confluent  in  cancerous  affections.  The 
jaundice  may  be  absolute,  but,  as  a  rule,  it  is  not  complete. 
Infective  cholangitis  and  infection  of  the  pancreatic  ducts 
are  commonly  present,  as  shown  by  the  temperature  and 
by  ague-like  seizures.  Although  the  loss  of  flesh  is  marked 
in  chronic  pancreatitis,  it  is  less  evident  than  in  cancer 
of  the  head  of  the  pancreas,  and,  until  the  disease  has 
existed  for  a  longer  time  than  cancer  gives  its  victim, 
there  is  no  sign  of  anasarca  or  ascites  or  of  enlarged  abdo- 


520      The  Pancreas:  Its  Surgery  and  Pathology 


)j'Wtr5un5 


minal  veins.  The  gall-bladder  is  seldom  distended,  though 
this  is  not  an  absolute  rule,  as  in  several  cases  we  have 
had  the  opportunity  of  observing  it  much  enlarged. 
Between  gall-stones  in  the  common  duct  and  chronic 
pancreatitis  (which  frequently  coexist)  it  is  often  difficult 
to  determine,  but  this  is  of  no  moment  from  a  practical 
point  of  view,  as  surgical  treatment  is,  as  a  rule,  demanded 
in  both  conditions.  Anaemia  is  much  more  marked  in 
cancer  of  the  head  of  the  pancreas  than  in  chronic  inter- 
stitial pancrea- 
titis. 

Cancer  of  the 
common  duct  is 
rare  and  is  usu- 
ally associated 
with  gall-stones ; 
if  the  disease  in- 
volves the  pa- 
pilla the  symp- 
toms are  indis- 
t  inguishable 
from  those  of 
cancer  of  the 
head  of  the 
pancreas;  but  if 
it  be  situated 
above  the  opening  of  the  pancreatic  duct,  it  will  not  inter- 
fere with  the  functions  of  the  pancreas,  and  therefore  the 
loss  of  flesh  will  not  be  so  rapid.  In  two  cases  of  cancer 
of  the  common  duct  in  which  we  have  made  an  analysis  of 
the  fseces  they  were  found  to  be  soft,  white,  and  friable, 
like  chalk  or  white  Castile  soap.  No  trace  of  stercobilin 
could  be  found  in  either  instance.  A  quantitative  estima- 
tion of  the  fats  showed  90  per  cent,  of  total  fat,  of  which 
32  per  cent,  was  neutral  fat  and  58  per  cent,  combined 
fatty  acid,  in  the  one  case,  and  total  fat  8^  per  cent., 


Fig.  172. — Diagram  showing  the  sites  of 
origin  of  malignant  disease  in  the  ducts  and 
ampulla  of  Vater  (modified  from  RoUeston). 


Neoplasms  521 

consisting  of  30  per  cent,  of  neutral  fat  and  53  per  cent,  of 
combined  fatty  acid,  in  the  other.  Suppurative  cholan- 
gitis is  occasionally  present,  but  this  is  not  a  constant 
event.  The  accompanying  diagram  shows  the  positions 
that  growths  may  occupy  in  the  neighbourhood  of  the 
papilla  (Fig.  172). 

Cancer  of  the  liver  is  distinguished  by  the  jaundice 
being  absent  or  much  less  intense,  and  by  the  enlarge- 
ment of  the  liver,  with  irregular  nodules  on  its  surface 
and  edges. 

In  simple  catarrhal  jaundice  the  symptoms  are  almost 
negative,  except  for  the  jaundice  and  loss  of  appetite ; 
and  the  way  in  which  it  yields  to  treatment  shows  the 
slighter  nature  of  the  ailment. 

In  cancer  of  the  pylorus  the  predominance  of  gastric 
symptoms,  the  dilatation  of  the  stomach,  with  absence  of 
free  hydrochloric  acid  and  the  presence  of  blood  in  the 
vomit,  usually  enable  a  diagnosis  to  be  made,  but  it 
should  not  be  forgotten  that  cancer  of  the  pylorus  and  of 
the  head  of  the  pancreas  frequently  coexist.  In  all  these 
cases  the  urinary  test  affords  most  valuable  help  in  diag- 
nosis. 

Treatment. — Medical  treatment  must  be  purely  sympto- 
matic :  morphine  if  needed  for  the  relief  of  pain ;  calcium 
chloride  for  the  prevention  of  hsemorrhage;  pankreon 
tablets  or  liquor  pancreaticus  for  the  digestion  of  food; 
and  other  remedies  for  symptoms  as  they  arise.  Surgical 
treatment  is  not  very  hopeful  and  has  usually  been  under- 
taken under  the  idea  that  the  cause  of  the  jaundice  might 
be  a  removable  one,  or  that  drainage  of  the  bile-ducts 
might  afford  relief  to  the  jaundice,  but  if  the  disease  has 
involved  the  head  of  the  pancreas  it  is  hopeless  however 
treated. 

Treatment  may  be  radical  or  palliative.  Ruggi,  of 
Bologna,  removed  through  the  loin  a  cancer  of  the  pan- 
creas weighing  23  ounces.     It  was  probably  growing  from 


522       The  Pancreas:  its  Surgery  and  Pathology 

the  tail  of  the  gland.  Complete  recovery  followed  and  the 
patient  was  well  for  three  months,  after  which  secondary 
disease  developed  and  the  patient  died  at  the  end  of  six 
months.  Professor  Ruggi  himself  has  kindly  furnished 
these  details.  Cades'  was  the  second  successful  case,  in 
1895,  a  tumour  of  the  tail  of  the  pancreas  of  the  size  of 
a  child's  head  being  removed.  Terrier,  in  1892,  removed 
a  tumour  weighing  five  pounds,  but  lost  his  patient.  Of 
sixteen  operations  for  removal  of  solid  tumours  of  the 
pancreas,  eight  recovered,  which,  considering  the  diffi- 
culty of  the  operation  and  the  depth  of  the  organ  to  be 
operated  on,  is  better  than  one  would  have  expected. 
Successful  pancreatectomies,  it  will  be  seen,  are  excep- 
tional and  are  feasible  only  where  the  growth  is  not 
involving  the  head  of  the  gland;  they,  however,  clearly 
demonstrate  that  a  tumour  of  the  body  or  of  the  tail  of  the 
pancreas  may  be  removed  with  equal  chance  of  recovery, 
and  should  the  disease  be  primary,  and  no  secondary 
growths  or  glandular  involvement  have  occurred,  great 
prolongation  of  life  is  quite  possible. 

The  palliative  operations,  cholecystotomy  and  cholecyst- 
enterostomy  for  the  relief  of  jaundice  in  cancer  of  the 
head  of  the  pancreas,  have  been  performed  by  one  of  us 
in  twenty-eight  cases,  all  the  patients  being  extremely 
ill  at  the  time  of  operation.  Many  of  these  cases 
occurred  when  there  was  difficulty  in  making  a  diagnosis 
between  cancer  of  the  head  of  the  pancreas  and  gall-stones 
in  the  common  duct,  or  between  cancer  and  interstitial 
pancreatitis,  difficulties  which  have  now  been  overcome 
to  a  large  extent.  Of  the  fifteen  cases  in  which  the  gall- 
bladder was  drained,  eight  recovered  from  the  operation, 
the  longest  survival  being  eight  months,  but  the  average 
survival  being  about  four  months ;  of  the  six  cholecysten- 
terostomies,  two  recovered  and  the  duration  of  life  was 
only  a  few  weeks.  Even  a  simple  exploratory  operation 
in  these  cases  is  attended  with  danger,  for  out  of  six  cases, 


Neoplasms 


523 


four  only  recovered  from  operation.  Dr.  Murphy,  of 
Chicago,  was  kind  enough  to  furnish  a  report  of  his  col- 
lected statistics  of  cholecystenterostomy  up  to  1897.  Of 
sixty-seven  non-malignant  cases  there  had  only  been 
three  deaths,  but  of  his  twelve  malignant  cases  ten  died, 
giving  a  mortality  of  83.3  per  cent.  Thus  it  will  be  seen 
that  any  palliative  operation  for  the  relief  of  cancer  of 
the  head  of  the  pancreas 
associated  with  jaundice  is 
useless,  as,  even  if  recovery 
occurs,  life  is  not  prolonged 
to  any  great  extent. 

Sarcoma. —  Primary  sar- 
coma of  the  pancreas  is 
undoubtedly  rare,  though 
secondary  '  disease,  espe- 
cially of  the  melanotic 
type,  seems  to  be  less  un- 
common. There  are  exam- 
ples of  sarcoma  in  several  of 
the  museums,  photographs 
of  some  of  which  are  shown 
in  the  illustrations.  The 
first  is  of  melanotic  sar- 
coma from  the  Hunterian 
Museum  (Fig.  173).  It  was 
taken  from  a  girl,  aged 
twenty  years,  and  was  sec- 
ondary   to    a    melanotic 

growth  in  the  eye,  which  was  removed  three  years  before 
her  death.  The  next  specimen  is  a  very  large  spindle- 
celled  sarcoma  from  University  College  Hospital  Museum, 
No.  3200  (Fig.  174).  The  growth  has  completely  de- 
stroyed the  gland  and  has  left  no  trace  of  gland  tissue. 
The  next  specimen  (Fig.  175),  No.  2836  A,  in  the  Royal 
College  of  Surgeons  Museum,  was  removed  from  the  tail 


Fig.  173. — Melanotic  sarcoma 
in  the  pancreas  (Royal  Coll.  of 
Surg.  Museum,  2836). 


524      The  Pancreas:  Its  Surgery  and  Pathology 

of  the  pancreas,  but  the  child  succumbed  shortly  after  the 
operation. 

Operation  for  sarcoma  of  the  pancreas  is  uncommon, 


Fig.   174. — Spindle-celled  sarcoma  of  the  pancreas  (Univ.  Coll.  Mu- 
seum, 3200). 


Fig.  175. — Sarcoma  of  the  tail  of  the  pancreas  (Roy.  Coll.  Surg.  Mu- 
seum, 2836  A). 

though  the  few  cases  operated  on  prove  that  if  the  tumour 
be  in  the  tail  of  the  pancreas  the  case  is  amenable  to  siu:- 


Neoplasms  525 

gical  treatment.  The  abdomen  was  explored  by  one  of  us 
in  a  case  of  the  kind,  but  the  disease  was  found  to  be  too 
extensive  for  removal.  Kronlein,  in  1894,  removed  a 
tumour  of  the  size  of  the  fist,  but  the  patient  died  seven 
days  later,  A  tumour  which  was  successfully  removed 
by  Briggs  proved  to  be  sarcomatous  degeneration  of  an 
echinococcus  cyst. 

Adenoma. — Adenoma  of  the  pancreas  is  extremely 
rare.  Instances  have  been  recorded  by  Thierf elder, 
Biondi,  Cesaris-Demel,  Neve,  and  Nicholls.  Several 
other  cases  described  as  adenomata  were  probably  exam- 
ples of  malignant  growths,  and  cannot  therefore  be  in- 
cluded in  the  list.  It  is  possible  that  some  of  the  cases 
described  as  cystadenomata  originated  in  simple  adenoma, 
but,  as  this  is  uncertain,  they  are  best  for  the  present 
considered  under  the  heading  of  cysts. 

Diagnosis  and  Treatment. — Adenomata  of  the  pancreas 
present  no  characteristic  symptoms  by  which  they  can  be 
distinguished  during  life,  but  should  such  a  tumoiu"  be 
met  with  in  the  pancreas  during  the  course  of  an  explora- 
tory operation  an  attempt  should  be  made  to  extirpate 
or  enucleate  it. 

Tuberculous  Disease  of  the  Pancreas. — Tuberculosis  of 
the  pancreas  is  usually  considered  to  be  rare,  and  as  a 
pirmary  lesion  it  undoubtedly  is,  but  Kudrewetzki  found 
that  in  a  series  of  one  hundred  and  twenty-eight  cases  of 
tuberculosis  the  pancreas  was  affected  fifteen  times,  five 
times  as  part  of  an  acute  miliary  tuberculosis,  seven  times 
as  part  of  a  chronic  tuberculosis,  and  twice  from  tuberculo- 
sis in  its  neighbourhood.  Children  furnished  the  greater 
number,  for  he  found  44.44  per  cent,  of  pancreatic  tuber- 
culosis in  tuberculous  children,  but  only  9  per  cent,  in 
adults.  He  emphasises  the  fact  that  tuberculosis  of  the 
pancreas  occurs  only  as  a  secondary  condition  in  connec- 
tion with  tuberculosis  of  other  organs.  In  Hale  White's 
series  of  one  hundred  and  forty-two  post-mortems  in  which 


526       The  Pancreas:  Its  Surgery  and  Pathology 

the  pancreas  appeared  to  be  diseased  or  injured  there 
were  four  examples  of  tubercle.  Three  of  the  patients 
suffered  from  general  tuberculosis  and  one  from  tubercu- 
lous peritonitis.  He  states  that  tubercle  of  the  pancreas 
was  found  in  considerably  less  than  i  per  cent,  of  all  cases 
of  tuberculosis,  and  he  therefore  considers  that  it  is  a  rare 
disease.  Loheac  would  explain  the  relative  infrequency 
of  tuberculous  disease  by  virtue  of  the  peculiar  pancreatic 
secretion,  which  he  thinks  to  be  protective  against  this 
form  of  infection. 

Tuberculosis  of  the  pancreas  may  occur  as  numerous 
small,  granular,  infiltrating  tubercles  or  as  large  caseous 
masses.  The  latter  probably  originate  in  most  cases 
from  lymphatic  gland  buried  in  the  substance  of  the  gland. 

Treatment. — A  few  cases  of  successful  removal  of  tuber- 
culous masses  from  the  pancreas  have  been  recorded. 
Thus  Sendler  opened  the  abdomen  of  a  thin  woman,  who 
had  a  movable  tumour  above  the  umbilicus,  and  found 
behind  the  stomach  a  hard  mass  the  size  of  a  walnut, 
which  he  extirpated.  This  proved  to  be  a  tuberculous 
lymph-nodule  of  the  pancreas.  The  patient  recovered, 
Kudrewetzki  reports  a  case  in  which  a  caseous  tubercu- 
lous mass  burst  into  the  stomach  of  a  man  of  forty-two. 
The  patient  was  operated  on  and  a  number  of  caseating 
glands  found  in  the  lesser  omentum,  but  he  became  so 
collapsed  on  manipulating  a  tumour  occupying  the  site 
of  the  head  of  the  pancreas  that  nothing  further  was 
done.     The  wound  healed  and  he  was  discharged. 

Symptoms  and  Diagnosis. — At  present  it  is  impossible 
to  diagnose  tuberculosis  of  the  pancreas  during  life,  and 
since  it  is  practically  always  secondary  to  disease  else- 
where, its  recognition  is  of  no  practical  importance  unless 
there  are  pressure  symptoms. 

Syphilis. — Syphilis,  like  tubercle,  may  occur  in  the 
pancreas  in  two  forms,  interstitial  and  gummatous, 
which  may,  however,  coexist.     Of  the  t\^o,  the  former  is 


Neoplasms  527 

the  more  common.  Both  may  result  from  either  acquired 
or  congenital  disease. 

In  acquired  syphilis  disease  of  the  pancreas  is  regarded 
as  uncommon,  but  this  may  be  due  to  there  being  no 
characteristic  symptoms  during  life,  in  most  cases,  point- 
ing to  the  pancreas.  There  is  no  reason  why  the  pancreas 
should  not  be  involved  with  other  organs  in  visceral 
syphilis,  which,  being  recognised  and  suitably  treated, 
recover,  for  a  gumma  of  the  pancreas  is  just  as  likely  to 
yield  to  treatment  as  gumma  of  the  liver.  Post-mortem 
records  with  regard  to  syphilitic  affections  of  the  pancreas 
are  but  meagre.  Peterson  in  eighty-eight  cases  that  had 
suffered  from  tertiary  syphilis  found  only  one  in  which  the 
pancreas  was  affected. 

Occasionally  syphilitic  disease  of  the  pancreas  may 
give  rise  to  secondary  symptoms ;  thus,  H.  Betham  Robin- 
son has  given  the  details  of  a  case  in  which  there  was 
obstructive  jaundice  due  to  a  gummatous  infiltration 
involving  the  head  of  the  gland,  in  which  cholecystoco- 
lostomy  was  successfully  performed. 

In  congenital  syphilis  the  pancreas  is  less  commonly 
affected  than  the  spleen  or  liver,  but  syphilitic  deposits 
have  been  noticed  as  early  as  the  fifth  month.  As  a  rule, 
the  disease  occurs  as  an  interstitial  inflammation  starting 
from  the  vessels,  but  occasionally  it  occurs  in  the  form 
of  large  or  small  gummatous  masses.  The  interstitial 
overgrowth  spares  the  islands  of  Langerhans,  so  that  dia- 
betes does  not  occur. 

Treatment. — The  surgical  treatment  of  syphilis  of  the 
pancreas  is  limited  to  such  cases  as  that  of  Betham  Robin- 
son above  referred  to,  and  reliance  must  be  placed  upon 
general  medical  means  for  dealing  with  this  disease. 

Literature 

Baudael:  Dissert.,  Freiburg,  1885. 
Biach:  Wien.  med.  Wochen.,  1883. 
Biondi:  Ref.  Med.,  1896;  Clin.  Chir.,  4,  1896. 


528       The  Pancreas:  Its  Surgery  and  Pathology 

Birch-Hirschfeld :   Arch.  d.  Heilk.,  xvi. 

Briggs:   St.  Louis  Med.  and  Chir.  Journ.,  1890,  p.  154. 

Brunton,  Lauder:    Brit.  Med.  Journ.,  June  11,  1904,  p.  1353. 

Cesaris-Demel :   Arch,  per  le  Soc.  m6d.,  1895,  xix. 

Codivilla:    Rendoconto  statist  d.  Sezone  Chih.  dell'  ospedale  de  mola, 

1898. 
Dovan:  Brit.  Med.  Journ.,  Oct.  22,  1904,  p.  1073. 
Dunning:   Amer.  Journ.  of  Obstetr.,  Jan.,  1905,  p.  161. 
Eppinger:   Prager  Vierteljahresschr.  f.  Heilk.,  cxiv. 
Fawcett:    Lancet,  May  7,  1904. 
Franke:   Arch.  f.  klin.  Chir.,  xliv,  1901. 
Hancock:  Journ.  Araer.  Med.  Associat.,  Jan.  27,  1906. 
Healey:   Journ.  of  Roy.  Army.  Med.  Corps,  iv,  3,  362. 
Kakels:  Amer.  Journ.  of  Med.  Sci.,  1902,  cxxiii,  471. 
Kronlein:  Weiner  med.  Wochen.,  1895,  S.  1318;  Beitrage  z.  klin.  Chir., 

1895, _S.  663. 
Kudrewetzki:   Prag.  Zeit.  f.  Heilk.,  1892. 
Lawrence:    London  Med.  Gazette,  1845,  xxxvi,  951. 
Loh6ac:   Quoted  by  Roswell  Park,  Amer.  Med.,  1903,  p.  949. 
Malcolm:    Lancet,  March,  1902. 

Malthe:   Zeitschr.  f.  Prof.  Herberg,  Kristiania,  1895. 
Martin:  Trans.  Path.  Soc.  of  Lond.,  1900. 
Monprofit:   Gaz.  m^d.  de  Paris,  March  12,  1904. 
Neve:   Indian  Med.  Rec,  1892,  p.  208;   Lancet,  1901,  p.  9. 
Nichelsohn:    Dissert.,  Wurzburg,  1894. 
NichoUs:  Journ.  of  Med.  Research,  viii,  2,  385. 
Nocard  and  Friedberger:    "Vet.  Path.,"  Friedberger  and  Frohner,  tr. 

Hayes,  1905. 
Opie:  "Diseases  of  the  Pancreas,"  1903. 
Oser:   Nothnagel's  "Encyclop.  of  Pract.  Med." 
Park,  Roswell:  Amer.  Med.,  v,  24,  949. 
Paulicki:   Allgemein  medicin  Centralzeitung,  1868,  No.  90. 
Peterson:  Monatshft.  f.  prakt.  Derm.,  1891. 
Phillips:   Lancet,  Feb.  16,  1907,  p.  418. 
Raven:   Brit.  Med.  Journ.,  Oct.  15,  1904,  p.  loii. 
Rhode:   Inaug.  Dissert.,  Keil,  1890. 
Robinson,  Betham:   Brit.  Med.  Journ.,  1900,  p.  1004. 
Robson,  Mayo:    Clin.  Soc.  Trans.,  1889,  xxiii;     Lancet,  July  2,   1900; 

Lancet,  March  19,  26,  and  April  2,  1904. 
Routier:  Rev.  de  Chir.,  1892. 

Segre:  Ann.  Univers.  della.  med.  e  chir.,  cclxxxiii. 
Sendler:  Deut.  Zeit.  f.  Chir.,  1896,  xliv. 
Schlagenhauf er :  Arch.  f.  Derm.  u.  Syph.,  1895. 
Schleisinger:   Virch.  Arch.,  cliv,  p.  501. 
Soyka:  Prag.  med.  Wochenschr. ,  Oct.,  1876. 
Stewart:   Brit.  Med.  Journ.,  April  16,  1904,  p.  885. 
Terrier:   Nimier:  Rev.  de  Chir.,  1893,  1894. 
Trendelenburg:   Deut.  Zeit.  f.  Chir.,  1886. 
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White,  Hale:    Guy's  Hosp.  Rep.,  1897,  liv,  26. 


INDEX  OF  AUTHORS 


AbELMANN,     208,     209,      210,      221, 
223,   267 

Abia,  165 

Abram,  306,  308,  309 

Acard,  303,  308 

Ackeron,  241,  267,  329,  344 

Adami,  95 

Adams,  471 

Addison,  256,  286,  302 

Alay,  500 

Aldehoff,  271,  308 

Alexander,  339 

AUbtitt,  317 

Allen,  359,  485,  486 

Alt,  194 

Ancelet,  164,  486 

Anders,  471 

Andrews,  471 

Anschiiltz,  303,  308 

Ansperger,  471 

Arnozan,  164 

Arris,  243,  268 

Aschoff,  296 

Auche,  370,  383 


Babler,  410 

Baillie,    140,    188,    361,   362,   383, 
4.7^,  4.86 


Baillie,    14c,    ^„„,    j„^,   j„_,   j„ 

473.  486 

Bainbridge,  98,  122,  124,  307,  308 
Baines,  410 
Baldi,  209,  237,  267 


Baldwin,  240,  267 

'"   ''  ""     190,    191,    192 


Balser,    141,    188,    ig 
194,  195,  205,  362 
Bancroft,  124 
Bandel,  527. 
Barcroft,  98 
Barling,  410,  471 
Barnard,  471 
Battersby,  332,  344,  471 
Baudach,  185 
Baudael,  188 

Bayliss,  96,  loi,  104,  105,  124 
Becker,  355,  357,  359 
Becourt,  47,  510 
Beddard,  307,  308 

34 


Benda,  194 

Bender,  194 

Bernard,  96,   112,   118,   119,   124, 

208,  225 
Bernheim,  171 
Bertram,  355,  359 
Biach,  527 
Bidder,  108,  124 
Bierry,  122 
Biondi,    187,    188,    234,   325,   344, 

525,  527 
Birch-Hirschfeld,    149,    161,    162, 

188,  374,  383.  528 
Birmingham,  28,  40 
Bloch,  279,  308 
Blum,  302,  308 
Blume,  197,  205 
Blumenthal,  242,  267,  275,  308 
Boas,  265,  267,  501,  510 
Boeckmann,  471 
Bohm,  76,  184,  188 
Boldt,  181,  188 
Borchardt,  355,  357,  359 
Borrell,  186,  188 
Bosanquet,    127,    164,    188,    273, 

279,    280,    281,    287,    288,    291, 

297,  308,  413,  425,  471 
Bouchardat,  269,  278,  308 
Bousfield,  380 
Bowditch,  264,  268 
Bozeman,  176,  188 
Bozenaum,  510 
Brachet,  44 
Brackel,  510 
Bramann,  355,  357,  359 
Bramwell,  131,  132,  188,  237,  268 
Braune,  29,  31 
Brennecke,  410 
Briggs,  185,  188,  525,  528 
Bright,  277,  308,  323,  344. 
Broadbent,  380 
Brodie,  123,  124 
Brown,  351,  359,  410 
Bruce,  287 
Briicke,  119,  124 
Brunn,  44 
Brunton,  528 


529 


53° 


Index  of  Authors 


Bryant,  410 

Bull,  176,  188,  325,  344,  510 

Bunger,  57,  63 

Bunting,  393,  410 


Cacchini,  55 

Cades,  522 

Cajal,  R.  y.  40 

Caldwell,  357,  359 

Cammidge,  243,  268,  334,  342,  344, 

395 
Capparelli,    271,    308,    325,    332, 

344,  481,  486 
Carnell,  355,  359 
Carnot,    142,    151,    153,    163,    164, 

188,  423,  471 
Cart  ledge,  510 
Castle,  266,  268 
Cathcart,_35i,  359 
Cavazzani,  209,  221,  268 
Cayley,  149,  188 
Cesaris-Demel,  187,  525,  528 
Cesaris-Deruch,  188 
Chalmers,  378,  471 
Chamberland,  103 
Chari,  325,  344 
Charles,  307,  308 
Chauffard,  299,  302,  303,  308 
Chiani,  188 

Chiari,  128,  191,  194,  205 
Chopart,  277,  308 
Choronschizky,  44 
Churton,  282,  317,  510 
Claessen,  56 
Clark,  264,  268 
Classen,  410 
Claus,  276 

Clayton-Greene,  106,  124 
Cleland,  259,  260,  261,  268 
Glutton,  510 
Codivilla,  528 
Cohnheim,  116,  124,  269,  275,  276, 

294,  307.  309 
Coivisart,  112,  124 
Cooke,  264,  268,  410 
Coombs,  351,  359 
Cooper,  347,  359 
Cotter,  471 
Courvoisier,  181,  188 
Cowley,    277,    309,    325,  344,  473, 

486 
Crofton,  274,  307,  309 
Cruveilhier,  510 
Cubert,  511 
Cumston,  505,  510 
Cunningham,  28 


Dale,  92,  93,  95 
Dalziel,  471,  483,  486 
Dargan,  357,  359 
Davian,  471 
Davidoff,  76 
Davidson,  477 
De  Renzi,  221,  268 
De  Witt,   26,   80,   81,   82,   83,   84, 
85,  87,  88,  90,  91,  93,  95,  293, 

309 
Deanesly,  410 
Deaver,  134,  146,  410,  471 
Delageniere,  475,  486 
Delbet,  471 
Delezenne,  113,124,  265,  353,359, 

501.  510 
Demme,  210,  268,  325,  344 
Desjardins,  152,  156,  188,  471,  472 
Dettmer,  196,  201,  205 
Deucher,  211,  268 
Diamare,  91,  95,  292,  294,  309 
Dieckhoff,  149,  150,  186,  188,  195, 

205,  282,  284,  286,  510 
Dixon,  510 
Dobrzycki,  56 
Dogiel,_  84,  95 
Dominicus,  236,  237 
Dovan,  528 
Drasche,  410 
Drozda,  163,  188 
du  Pasquier,  511 
Dunning,  177,  188,  510,  528 
Duponchel,  510 
Durante,  510 
Durno,  410 
Dutil,  184,  188 
Dutourier,  303,  309 
Duval,  157,  189,  471 


Earl,  410 
Eberle,  118,  124 
Ebner,  79,  8i,  83,  85,  95 
Ecker,  47,  63 
Edgecombe,  373,  383 
Edie,  306,  309 
Edsall,  233,  268 
Ehler,  471 
Ehrlich,  275 
Eichhorst,  483,  486 
Elliotson,  264,  268,  277, 
Embden,  276 
Engel,  49,  63,  510 
Eppmger,  513,  528 
Ernst,  195 
Estes,  471 
Eulenberg,  486 


309 


Index  of  Authors 


53^ 


Evans,  471 

Ewald,  113,  339,  344 


Fawcett,  204,  205,  528 

Fehling,  267,  283 

Felix,  44 

P^enwick,  66,  67 

Filger,  188 

Fischer,  115 

Fisher,  510 

Fison,  190,  191,  394,  396,  410 

Fitz,  126,  141,  149,  188,  195,  196, 

205,    287,    324,    344,    359,    362, 

383,  386,  399,  410,  471,  510 
Fleig,  105 

Fleiner,  164,  188,  291,  309 
Fles,  222,  277,  309,  323,  328,  344 
Fletcher,  410 
Flexner,  141,  142,  145,   150,  151, 

157,    158,    159,    188,    197,    201, 

202,  205 
Flint,  72,  84,  85,  86,  95 
Fraenkel,  195,  202,  205 
Franke,  528 
Freidenthal,  143 

Frerichs,  277,  279,  280,  284,  309 
Frey,  124 

Friedberger,  471,  512,  528 
Friederich,  410 
Friedrich,  135,  188 
Fripp,  410 
Frison,  410 
Frohner,  471,  528 
Fromme,  339,  344 
Fuchs,  410 

Gachet,  113 
Gaeia,  486 
Gale,  243,  268 
Galea,  473 
Galippe,  171,  172 
Gallaudet,  65 
Gamgee,  123 
Gamges,  471 
Garre,  345 
Gaston,  463 
Gaule,  77 
Gaylord,  296 
Gegenbaur,  50,  63 
Generisch,  47,  63 
Gentes,  297,  309 
Gerhardi,  234,  268 
Gerhardt,  188 
Giacco,  275 
Gilbert,  510 
Giordano,  471 


1S8,  332,  474, 


Glaessuer,  108,  109,  124 
Glinski,  46,  49,  50,  53,  54,  63 
Goldmann,  349,  359 
Golgi,  74,  81,  84 
Goodall,  181,  188 
Goodman,  325,  344 
Goppert,  44 
Gordon,  226,  268 
Gosset,  471 
Gotte,  44 
Gottlieb,  199,  205 
Gould,  325,  344,  483,  486 
Gourand,  510 
Gow,  79,  80,  95 
Graaf,  486 
Graham,  510 
Greisclius,  411 
Greville,  45  8 
Groeningen,  349,  359 
Griiber,  160 
Guidiceandra,  172 

486 

Guinard,  368,  383 
Gulcke,  200,  205 
Guleke,   143,    148,   151,    188,   287, 

309 
Giinther,  19,  27 
Giissenbauer,  500,  510 
Guyose,  458 

Hadra,  351,  359 

Hagen,  510 

Hagenbach,  175,  188,  510 

Hahn,  355,  357,  359,  411 

Haldane,  263,  268 

Halley,  411 

Halliburton,  123,  124 

Halstead,  144,  366,  383,  3S9,  400, 

411 
Ham,  259,  260,  261,  268 
Hamburger,  44 
Hammar,  44 
Hammarschlag,  277,  309 
Hammarsten,  97,  124,  125 
Hancock,  528 
Hanot,  302,  303,  309 
Hansemann,   51,   88,   91,   95,   129, 

130,  131,  162,  188,  194,  205,  279, 

280,  281,  286,  299,  359 
Hardin,  471 

Harley,  271,  309,  325,  329,  463 
Harris,  79,  80,  95 
Hartmann,  177,  188,  511 
Hartsen,  277,  309 
Harvey,  411 
Hawkins,  149,  188,  402 
Hayes,  471,  528 


532 


Index  of  Authors 


Haynes,  511 
Healey,  185,  188,  528 
Heaton,  411,  511 
Hedon,  236,  271,  309 
Heidenhain,  77,  92,  98,   100,   113, 

199,  205 
Heinricus,  173,  174,  188 
Heller,  194,  205 
Helly,  44,  52,  54,  57,  63,  144,  257, 

319.  365-  383 
Hennige,  268 
Hennigs,  188 
Hennings,  135 
Herberg,  528 
Hermann,  125 
Herter,    108,    125,   207,   224,    233, 

240,  267,  268,  302,  309,  500,  511 
Hertz,  55 

Herxheimer,  300,  309 
Herzen,  113 
Herzog,  295,  297,  309 
Hess,  142,  143,  188 
Hewlett,  268 
Hildebrand,    196,    197,    200,    201, 

205 
Hill,  125 
Hillier,  181,  188 
Hirschfeld,  221,  325,  344 
Hlava,  142,  188,  196,  20T,  205 
Hodgkin,  188 
Hofmeister,  112 
Hogarth,  411 
Hollander,  511 

Holzmann,  332,  344,  480,  486 
Hoppe,  176,  188,  511 
Hoppe-Seyler,   164,   188,   291,  309 
Horrocks,  511 
Hufeland,  344 
Hyrtl,  49,  63 


Jaboulay,  471 
Jackson,  195 
Jacob,  370,  383 
Jacobson,  176,  189,  411 
Jaksch,  501,  511 
Jankelowitz,  44 
Jarotzky,  91,  92,  95 
Jastrowitz,  241,  268 
Jaun,  349,  352,  359 
Jeanselme,  303,  309 
Jeffrey,  411 
Jephson,  355,  357,  359 
Johnston,  474,  475,  486 
Jones,  411 
Joslin,  295,  310 
Jung,  196,  205 


Kakels,  185,  189,  528 

Karewski,  351,  355,  359 

Kasahara,  87,  95,  162,  1S9 

Katz,  197,  201,  205,  210,  234,  268 

Kauffmann,  277,  309 

Kausel,  271 

Keenan,  189 

Kehr,  471 

Keiserling,  387 

Keith,  42,  43,  45 

Kellock,  511 

Kelly,  339,  344 

Kempe,  403,  411 

Kennan,  149,  411 

Keyser,  411 

Kilgow,  411 

Kindt,  355,  356,  360 

Kinnicutt,  172,  1S9,  479,  482,  486 

Klebs,  56,  175,  189,  309 

Kleburg,  357,  359,  360 

Klippel,  165,  189,  471 

Klob,  so,  51,  53,  63,  411,  sii 

Klobin,  49 

Kocher,  66,  466 

Kolliker,  95 

KoUmann,  41 

Korte,  69,  108,  149,  150,  151,  178, 
179,  189,  195,  197,  202,  205,355, 
359,  360,  400,  411,  471,  481,  486, 

500.  511 
Kossel,  125 
Krehl,  268 

Kronlein,  70,  185,  525,  528 
Kudrewetzki,  525,  526,  528 
Kiihn,  184,  189 
Ktihnast,  511 
Kiihne,  77,  83,  95,  113,  115,  123, 

125,  482 
Kiilenkampff,  351,  360 
Kuliabko,  294,  309 
Kiilz,  242,  268 
Kummell,  482 
Kuntzmann,  323,  325,  344 
Klister,  89,  95,  320,  329,  344,  351, 

360 
Kutscher,  116 
Kiittner,  357,  360 
Kyber,  135 


Laborderie,  357,  359 

Lacher,  56 

Laguesse,  45,  85,  87,  88,  89,  93,  95, 

292,  309 
Lancereaux,    144,    150,    186,    188, 

189,    269,    277,    278,    309,    480, 

486 
Langendorff,  152,  271 


Index  of  Authors 


533 


92, 195, 196, 201, 202, 205, 240, 
174, 286, 289, 290, 292, 293, 294, 
95, 296, 297, 299, 300, 303, 366, 

374, 396,  417, 426, 447,  449, 515, 

527 . 

Lannois,  165,  189,  291,  309 

Lapasset,  370,  383 

Lawrence,  528 

Le  Nobel,  241,  268,  325,  329,  344 

Lea,  77,  84,  95,  482 

Lefas,  165,  189,  424,  471 

Leichtenstern,  332,  344,  479,  486 

Leith,  349,  352,  360 

Lejars,  471 

Leraione,  165,  189,  291,  309,  370, 

383 
Lenne,  309 
Lens,  63 
Leonhard,  196 
Lepage,  100,  102,  125 
Lupine,    165,    241,   268,    274,    275, 

297,  309 
LetuUe,  52,  53,  59,  181,  189 
Leusden,  411 

Lewaschew,  84,  88,  92,  93,  95 
Lewis,  51,  S3 
Lichtheim,  329,  344 
Lilienthal,  411 
Littlewood,  351,  360 
Lloyd,  68,  178,  189,  351,  360,  511 
Loevenhart,  266,  268 
Loewi,  116 
Loheac,  526,  528 
Lophius,  87 
Lorand,  274,  309 
Lorrier,  59 
Lowe,  471 
Lubarsch,  185 
Ludolph,  332,  344,  511 
Lund,  411 
Lynn,  511 

Macaigni,  285 
Macallum,  78,  95 
Mackenzie,  379 
Mahomed,  471 
Malcolm,  506,  511,  528 
Mallory,  72,  86,  95 
Malthe,  528 
Maly,  125 
Mandel,  124 
Mankowski,  90,  93,  95 
Mann,  355,  360 


.04, 


Manprofit,  511 

Marcy,  471 

Margain,  303,  309 

Markuse,  271 

Marseron,  511 

Martin,  511,  528 

Martinotti,  269 

Matani,  479,  486 

Mayo,  163,  189,  362,  411,  471 

McPhedran,  489,  511 

McReynolds,  5 1 1 

Meckel,  51,  52 

Megnin,  415,  471 

Melzer,  112,  125 

Mering,  126,  189,  269,  270,  309 

Mett,^266,  267 

Michelsohn,  185,  189 

Mikulicz,  66,  403,  465 

Milisch,  197,  199,  205 

Milroy,  475 

Minkowski,    126,    189,    208,    23 

269, 270, 271,  272,  273,  274,  30 . 

306,  309 
Minnich,  332,  344,  479,  480,  481, 

486 
Minot,  81 

Monprofit,  177,  189,  528 
Moore,    261,    306,    309,    339,    344, 

411,  471 
Morache,  164 
Morgagni,  473,  486 
Morian,  411 
Morton,  511 
Mosetig-Moorhof,  471 
Motta,  325 
Moxon,  348,  360 
Moynihan,     160,    179,     189,     351, 

387,    411,    471,    475,    483,    486, 

509.  511 

Moyse,  47 

Mraczek,  162 

Miiller,  35,  40,  75,   120,   134,   146, 

162, 211, 222,  223, 225, 268, 410, 

471 
Munk,  119,  143,  277,  309 
Munster,  411 
Murphy,  444,  468,  523 
Murray,  511 
Muspratt,  403,  411 
Myles,  471 


Narath,  511 

Nash,  288,  308,  309,  351,  359 
Nauwerck,  51,  63 
Neuberg,  97,  125,  251,  268 
Neumann,  51,  53,  63,  511 
Neve,  187,  189,  525,  528 


534 


Index  of  Authors 


Nichelsohn,  528 

NichoHs,    51,    63,    187,    189,    525, 

528 
Niemann,  355 
Nimier,  172,  189,  528 
Nini,  355,  356,  357,  360 
Nocard,  415,  471,  512,  528 
Nocolaider,  77 
Noorden,  238,  301,  304,  309 
Norris,  411 
Nothnagel,    189,    268,    344,    387, 

411,  486,  511,  528 
Nussbaum,  463 


OcHSNER,  511 

Oddi,  38 

Oidtmann,  97,  125 

Olivier,  186 

Olt,  205 

Opie,  37,  38,  45,  50,  51,  5 
55,  59,  60,  61,  63,  78,  8 
92,  95,  131,  135,  136, 
145.  147.  153.  157.  161, 
165,  166,  189,  197,  198, 
201,  204,  205,  263,  266, 
280,  287,  290,  292,  295, 

300.  303,  309-  335>  336, 
366,367,383,386,389, 
413,  419,  424,  425,  471 

Orth,  149,  186,  189 

Oser,  139,  150,  184,  186, 
201,  205,  210,  211,  268, 
282,  285,  287,  324,  329, 
471,  474,  486,  511,  528 

Osier,  411 

Otis,  355,  357,  359,  360, 

Owen,  20,  21,  22,  23,  24,  27,  471 


Pagenstecher,  467 

Paltauf,  511 

Panarol,  473,  486 

Park,  486,  511,  513,  528 

Pauchet,  411 

Paulicki,  528 

Pavy,  276,  309 

Pawlik,  511 

Pawlow,  96,  98,  99,  100,  loi,  104, 
106,  108,  109,  no,  113,  120,  121, 
123,  125,  152,  189,  266,  267,  268 

Pearce,  89,  95,  142,  188 

Pearson,  63 

Peiser,  411 

Pende,  170,  172,  189 

Pensa,  80,  81,  95 

Pepper,  511 

Percival,  140,  189,  362,  383,  411 


2,  53 

,  54 

7.  9c 

.  91 

137- 

144 

162, 

164 

199, 

200 

268, 

279 

297- 

298 

342, 

344 

393- 

411 

,528 

187, 

197 

279- 

281 

344. 

387 

Pereira-Guimaraes,  359,  360 
Perle,  411 

Perowoznikoff,  120,  125 
Perrin,  471 
Peters,  511 
Peterson,  527,  528 
Phillips,  486,  494,  512,  528 
Phulpin,  511 
Pisenti,  233,  268 
Pitchford,  511 
Pitt,  176,  189,  411 
Plimmer,  122,  123,  125 
Pochon,  113 
Ponfick,  195,  205 
Popielski,  100,  123,  125 
Portal,  140,  362,  383,  4 
Portel,  189 
Porter,  403 
Poucet,  511 
Pressel,  348,  360 
Prince,  359,  360 
Przewoski,  511 
Pye-Smith,  511 


II 


QuAiN,  40,  45 
Quenu,  157,  i^ 


471 


Rachford,  27,  119,  120,  125 
Radziejewski,  120    ' 
Randall,  351,  352,  354,  360 
Ranschoff,  511 
Ravant,  299,  308 
Raven,  471,  528 
Raynes,  471 

Recklinghausen,  277,  302,  309 
Reed,  309 
Reeves,  325,  344 
Reichert,  63 
Renant,  89 

Rennie,  87,  95,  294,  309 
Rentoul,  132,  189 
Renzi,  234,  268 
Reynolds,  411 
Rhode,  528 
Riboli,  411 
Richards,  302,  309 
Richardson,  511 
Riedel,  154,  155,  189,  471,  511 
Rispal,  500 
Roaf,  339,  344 

Robinson,  163,  189,  511,  527,  528 

Robson,  68,  189,  268,  344,  351, 

362,  383,  396,  411,  468,  472,  486, 

509-  511 
Roddick,  411 


Index  of  Authors 


535 


Rodocanachi,  472 

Rokitansky,  135,  189 

Rolleston,   51,   63,   161,   358,   360, 

520 
Rose,  56,  360 
Rosenberg,  209,  268 
Rosenheim,  241,  268 
Ross,  351 
Roth,  51 
Routier,  528 
Rouxj  177,  189,  511 
Ruggi,  521,  522 

Sahli,  338,  339,  342,  343.  344 

Salkowski,  241,  242,  268 

Salomon,  220,  268 

Salzer,  511 

Sandmeyer,    151,    189,    209,    221, 

268,  272,  309 
Sanitas,  355,  360 
Santorini,  44,   52,   55,   60,   61,   62, 

145,  152,  156,  157.  171.  173.367. 

419,  420,  421,  470,  484,  485,  520 
Santos,  47,  48,  63,  203,  346,  415 
Sauerbeck,  93,  95,  271,  299,  309 
Saunby,  135,  139 
Saviotti,  74 
Sawyer,  196,  204,  205 
Scatterby,  317 
Schafer,  45,  125,  292,  309 
Schaffer,  74.  95 
Schafter,  40 
Schepowalnikow,  113 
Schieffer,  27 
Schiff,  113 

Schlagenhaufer,  234,  268,  528 
Schlesinger,  161,  162,  189,  528 
Schmidt,  106,  107,  108,  109,  124, 

125,  205,  212,  222,  268,  293, 297, 

300,  309,  330,  344 
Schmieden,  472 
Schroeder,  263,  268 
Schulze,  91,  93,  95,  152,  189,  293, 

309 
Scott,  93,  94,  95,  192, 193,  240, 268, 

300 
Seegen,  279,  310 
Segond,  472 

Segv6,  185,  189,  513,  528 
Seitz,  149,  189,  19s,  205,  287 
Selberg,  411 

Sandler,  163,  189,  472,  526,  528 
Senn,  151,  163,  172,  189,  207,  351, 

360,  470,  472,  488,  511 
Shattock,  475,  486 
Shaw,  511 
Shea,  411 


Sheen,  351,  360,  511 

Shirmer,  47,  50,  62,  63 

vShupmann,  479 

Silver,  277,  310,  325,  344 

Simmonds,  355,  360 

Simoni,  383 

Simonin,  369 

Slavsky,  355,  357,  360 

Smith,  383,  411,  467 

Soxhlet,  211 

Soyka,  528 

Spalteholz,  72,  84 

Ssobolew,   93,    95,    152,   189,   240, 

293,  297,  300,  310 
Stangl,  297,  298,  310 
Starling,  96,  98,  loi,  102,  103,  104, 
105,  107,  III, 113, 117, 124, 125, 
207,  307,  310 

Statkewitsch,  95 

Stefanani,  234,  268 

Steinhaus,  78,  95 

Sterling,  268 

Steven,  195,  205 

Stewart,  411,  516,  528 

Stibler,  315 

Stieda,  511 

Stoerk,  347,  360 

Stohr,  45 

Stokes,  212 

Stolnikow,  268 

Stoss,  45 

Strasburger,  229,  268 

Strauss,  270,  310 

Symington,  40,  47,  63 

Tait,  288 

Telling,  50,  51 

Terrier,  472,  522,  528 

Testut,  34.  35.  37.  39.  40,  57.   58. 

66,  365,  383,  491 
Thierf elder,  187,  525 
Thiroloix,  171,  173,  174.  189,  236, 

306,  310,  511 
Thomas,  411 
Thompson,  27,  359,  360 
Thomson,  132 
Tiedemann,  47 
Tieken,  47 
Tilger,  176,  179,  511 
Toye,  411 
Travers,  347,  360 
Trendelenburg,  528 
Trevor,  145,  189,  300,  310,  395 
Triconi,  528 
Truhart,  337,  344>  359 
Tuckett,  274,  310 
Tuffier,  472 


536 


Index  of  Authors 


Tulpius,   140,   189,  264,  268,  362, 

383 
Turner,  51,  53,  63 


Umber,  275,  310 
Underbill,  276,  310 


Van  den  Valden,  339 

Vasilieff,  123 

Vater,  59,  62,  70,  144,  145,  152, 
154,  15s,  156,  174,  315,  319,  365, 
366,  367,  379,  385,  389,  393,  394, 
395,  418,  419,  422,  481, 483, 485, 
486,  489,  520 

Vernon,  116,  125 

Vidal,  47,  63 

Villar,  471,  511 

Villi^re,  360 

Villiers,  349 

Virchow,  63,  95,  175,  188,  189, 
268,  309,  310,  498,  511,  528 

Vogel,  242,  268, 

Volhard,  117 

Volker,  45 

Von  Ackeron,  241,  267,  329,  344 

Von  Bramann,  355,  359 

Von  Ebner,  79,  81,  83,  85,  95 

Von  Frey,  124 

Von  Jaksch,  501,  511 

Von  Mering,    126,    189,   269,    270, 

309 
Von  Mikulicz,  66,  403,  465 
Von  Noorden,  238,  301,  304,  309 
Von  Recklinghausen,  277,  302,  309 
Vulpian,  164 


Wagner,  50,  63 
'Wagstaff,  349,  352,  360 
Walker,  226,  268 
Wallenfang,  339,  344 
Walther,  109,  120,  123,  472 
Wandesleben,  358,  360 
Watkins,  511 
Webber,  411 
Weichselbaum,  50,  51,  53,  63,  297, 

298,  310 
Weinland,  121,  122,  125 


Weintraud,  211,  221,  268,  271,  310 

Welch,  195,  196 

Wertheimer,    100,    loi,    102,    105, 

125 
White,    126,    150,    165,    185,    186, 
188,  189,  348,  349, 360, 413, 472, 

487,  511.  525.  528 
Widal,  160 
Wiener,  472 
Wilks,  348,  360 
Willcox,  262,  268,  340,  344 
Williams,  194,  197,  205 
Williamson,    131,    189,    279,    280, 

281,  284,  286,  300,  310 
Willie,  305,  338,  344 
Windle,  279,  280,  310 
Winkler,  197,  201,  205 
Winniwarter,  463 
Winslow,   47,   178,   351,   353,  358, 

391.  442 
Wirsung,  43,  44,  53,  57,  58,  60,  61, 
62,  72,  108,  141,  144,  152,  154, 
156,  157.  158,  159.  170.  171.  173. 

181,  182,  194,  210,  211,  235,  271, 
319.367.379.395.396,409,418, 
419,  420,  421,  470,  474,  482,  483, 
484,    485,    488,    489,    498,    520 

Wlassow,  45 

Wohlgemuth,   109,   113,   114,   118, 

123,  125,  501,  511 
Woolsey,  232,  268,  403,  411 
Wright,  52,  53,  63,  140,   230,  295, 

310 
Wyss,  57,  511 


Young,  237,  268,  411 


Zawadsky,  108,  125 
Zawarykin,  119,  125 
Zeehuisen,  501 
Zeigler,  63,  149 
Zeller,  472 
Zenker,  51,  54,  63 
Ziehl,  210,  268,  325,  344 
Ziemssen,  410 
Zimmermann,  45 
Zukowski,  511 
Zung,  93,  95 


INDEX 


Abdominal  salivary  gland,  71 
Abscess  of  pancreas  and  suppura- 
tive pancreatitis,  150 
pyemic,  of  pancreas,  150 
Absence  of  islands  of  Langerhans 

in  diabetes,  297 
Accessory  duct,  38 
pancreas,  49 
pancreatic  duct,  44 
Acetone   bodies   in   urine    in   dis- 
eases of  pancreas,  237 
Acne  pancreatica,  175 
Adenoma,  fibro-,  of  pancreas,  187 
of  pancreas,  187,  525 

diagnosis  and  treatment,  525 
Alcohol,  influence  of,   in  produc- 
tion of  pancreatitis,  160 
relation  of,  to  chronic  pancrea- 
titis, 424 
Alcoholism  in  diabetes,  301 
Alimentary  glycosuria  after  par- 
tial extirpation  of  pancreas, 
271 
from    disturbances    of    pan- 
creas, 304 
in    diagnosis    of    diseases    of 

pancreas,  337 
relation  of  pancreas  to,  305 
Alveoli  of  pancreas,  76 
Amphopeptone,  115 
Ampulla  of  Vater,  37,  39 

mode  of  formation,  59 
Amyloid     degeneration     of     pan- 
creas, 135 
Amylopsin,  1 1 1 

Anatomical     anomalies     of     pan- 
creas, 46 
variations  of  pancreatic  ducts, 
56 
Anatomy,    comparative,    of   pan- 
creas, 17 
of  pancreas,  28 
surgical,  of  pancreas,  64 
Anomalies,    anatomical,    of    pan- 
creas, 46 
Anthropoidea,  pancreas  of,  26 
Antipeptone,  115 


Apoplectic  cysts  of  pancreas,  175, 

506 
Apoplexy,  pancreatic,  138 
Appetite,    alterations    of,    in   dis- 
eases of  pancreas,  320 
Aquatic   mammals,    pancreas    of, 

24 
Areas  of  Langerhans,  78 
Arteries  of  pancreas,  32,  33 
Arteriosclerosis  in  diabetes,  301 
Atrophy  of  islands  of  Langerhans 
in  diabetes,  297 
of  pancreas,  129 
cachectic,  130 
in  diabetes,  129,  280 
secondary,  133 
Auto-intoxication   theory   of   dia- 
betes, 273 
Azotorrhea  in  diseases  of  pancreas, 

328   .     . 
Azoturia  in  diseases  of  pancreas, 
236 


Bacteria  as  cause  of  chronic  pan- 
creatitis, 151 

Bauchspeicheldruse,  71 

Bile  in  urine  in  diseases  of  pan- 
creas, 235 

Bile-duct,  common,  and  head  of 
pancreas,  operation  for  explor- 
ing, 458 

Bile-pigments,  relation  of  urobi- 
linuria  to,  in  diseases  of  pan- 
creas, 235 

Biliary  passages,  diseases  of,  asso- 
ciation of  diseases  of  pancreas 
with,  144 

Birds,  pancreas  of,  22 

Black  jaundice  in  diseases  of  pan- 
creas, 320 

Blood    changes   from   diseases    of 
pancreas,  230 
in  diabetes,  274 

in  feces  in  diseases  of  pancreas, 
332 


537 


538 


Index 


Blood-supply  of  pancreas,  32 

alterations    in,    as    cause    of 

chronic  interstitial  changes, 

164 
Bronzed  diabetes,  302 
Bullet  wounds  of  pancreas,  355 

symptoms,  356 

treatment,  356 


Cachectic   atrophy  of  pancreas, 

Calcium  oxalate  in  urine  in  dis- 
eases of  pancreas,  239 
Calculi,  pancreatic,  169,  473 

composition  of,  475 

glycosuria  in,  480 

in  diabetes,  281 

symptoms  of,  479 

treatment  of,  482 
Cammidge's    reaction    as    symp- 
tom of  diseases  of  pancreas,  334 
Canals,  Saviotti's,  74 
Carbohydrates  in  urine  in  diseases 

of  pancreas,  240 
Carcinoma    of   liver    and    chronic 

pancreatitis,     differentiation, 

431 
of  pancreas,  180,  505,  512 

and  chronic  pancreatitis,  dif- 
ferentiation, 340,  429 
differential  diagnosis,  517 
in  diabetes,  283 
secondary,  186 

deposits  from,  184 
symptoms,  514 
treatment,  521 
Carnivora,  pancreas  of,  24 
Caruncula  major,  36 

minor,  39 
Casein,  pancreatic,  128 
Cat,  pancreas  of,  25 
Catarrh  of  pancreas,  374 
pancreolithic,  473 
suppurative,  of  pancreas,  378 
Celiac  neuralgia,  215 
Cell-clumps,  intertubular,  78 
Cells,  centro-acinar,  78 
Centro-acinar  cells,  78 
Chemical  pathology  of  pancreas, 

206 
Chlorides  in  urine  in  diseases  of 

pancreas,  237 
Cholecystenterostomy,  463 
Cholelithiasis.      See  Gall-stones. 
Cirrhosis  of  liver,  pancreas  in,  165 

of  pancreas,  416 
Collagen,  117 


Comparative  anatomy  of  pan- 
creas, 17 

Connective  tissue  of  pancreas,  ar- 
rangement of,  71 

Cystadenoma    of    pancreas,     177, 

Cystic  disease,  congenital,  of  pan- 
creas, 177,  509 
epithelioma    of    pancreas,    177, 

50s 
neoplasms  of  pancreas,  176 
simple  tumors  of  pancreas,  505 
Cysts,  apoplectic,  of  pancreas,  175, 

506 
hemorrhagic,  of  pancreas,  509 
hydatid,  of  pancreas,  177,  510 
of  pancreas,  172,  487 

and  trauma,  relation  of,   179 

contents,  500 

diagnosis,  497 

digestive  power  of  fluid,  500 

etiology,  488 

in  diabetes,  282 

physical  signs,  492 

shape,  498 

statistics,  504 

symptoms,  490 

termination,  502 

treatment,  502 
statistics  on,  504 
proliferation,  of  pancreas,   176, 

505 
pseudo-,  of  pancreas,  178 
retention,  of  pancreas,  175 


Degeneration,  amyloid,  of  pan- 
creas, 135 
fatty,  of  pancreas,  134 

in  diabetes,  281 
hyaline,    in   islands   of   Langer- 
hans,  in  diabetes,  295 
of  pancreas,  135 
Diabete  bronze,  302 
gras,  278 
maigre,  278 
Diabetes,  269 

absence   of   islands   of   Langer- 

hans  in,  297 
acute  pancreatitis  in,  287 
after    extirpation    of   pancreas, 

269,  270 
alcoholism  in,  301 
arteriosclerosis  in,  301 
as  symptom  of  diseases  of  pan- 
creas, 333 
atrophy   of  islands   of   Langer- 
hans  in,  297 


Index 


539 


Diabetes,  atrophy  of  pancreas  in, 
129,  280 
auto-intoxication  theory  of,  273 
blood  in,  274 
bronzed,  302 

cancer  of  pancreas  in,  283 
chronic  interstitial  pancreatitis 

in,  289 
cysts  of  pancreas  in,  282 
dependence  of,  upon  disease  of 

pancreas,  269 
diminished    number    of   islands 

of  Langerhans  in,  297 
disease  of  solar  plexus  as  cause 

of,  272 
fatty  degeneration  of  pancreas 
'     in,  281 
gout  in,  301 
hemorrhage    into    pancreas    in, 

287 
hyaline  degeneration  in  islands 

of  Langerhans  in,  295 
infectious  natvire  of ,  2  7  7 
inflammatory   changes   in   pan- 
creas in,  286 
interacinar  pancreatitis  in,   292 
nervous   system   in   production 

of,  276 
pancreatic  calculi  in,  281 

extracts  in,  306 
pathological  changes  in  interaci- 
nar islets  in,  295 
secretin  in,  306 

swelling  and  increase  in  size  of 
islands  of  Langerhans  in,  299 
syphilis  in,  301 
treatment  of,  305 
Diabetes  bronze,  166 
Diagnosis,  general,  of  diseases  of 

pancreas,  311 
Diastase,  pancreatic,  in 
Diastatic     ferment,     method     of 
testing  for,  in  diseases  of  pan- 
creas, 267 
Digestion      glands     of      animals, 
comparative  anatomy,  17 
impaired,  of  starchy  foods,  re- 
duction or  failure  of  pancrea- 
tic secretion  as  cause,  223 
of  fat  by  pancreatic  juice,  117 
Digestive   disturbances   from   ab- 
sence or  diminution  of  pan- 
creatic secretion,  208 
enzymes  of  pancreatic  juice,  in 
functions  of  pancreas,  97 
symptoms   in   diseases   of  pan- 
creas, 320 
Diverticulum  of  Vater,  37,  39 


Dog,  pancreas  of,  25 
Duct  of  Santorini,  38,  44 

of  Wirsung,  36,  44 

pancreatic,  accessory,  44 
Ducts  of  pancreas,  36 

pancreatic,     anatomical    varia- 
tions of,  56 
Dyspepsia  in  diseases  of  pancreas, 

320 
Dyspeptic  disturbances  in  chronic 

pancreatitis,  428 


Emaciation   in  diseases   of  pan- 
creas, 320 

Embryology  of  pancreas,  41 

Enterokinase,  1x3 

Enzymes,  digestive,  of  pancreatic 
juice,  III 
pancreatic,  detection  of,  264 

Epithelioma,   aj'stic,  of   pancreas, 

177'  505 
Erepsin,  116 

Erythrocytes  in  pancreatitis,  231 
Ethereal    sulphates    in    urine    in 

diseases  of  pancreas,  233  _ 
Extirpation  of  pancreas,  diabetes 
after,  270 
partial,    alimentary    glycosu- 
ria after,  272 
glycosuria  after,  271 
utilisation   of   proteids   after, 


Fat,   digestion  of,   by  pancreatic 
juice,  117 
in  feces  in  diseases  of  pancreas, 

210,  211 
necrosis  in  diagnosis  of  diseases 
of  pancreas,  337 
of  pancreas,  190 

and  bacterial  invasion,  195 

experimental       production 

of,  196 

Fat-splitting  ferment  in  diseases 

of     pancreas,     method     of 

testing  for,  266 

in     urine     in     diagnosis     of 

diseases  of  pancreas,  335 

in  diseases  of  pancreas,  263 

Fatty   degeneration   of   pancreas, 

134 
in  diabetes,  281 
feces  in  diseases  of  pancreas,  323 
infiltration  of  pancreas,  134 
Feces,  blood  in,  in  diseases  of  pan- 
creas, 332 


540 


Index 


Feces,  fat  in,  in  diseases  of  pan- 
creas,  2IO,  211 
fatty,   in  diseases  of  pancreas, 

.    323      . 

in  chronic  pancreatitis,  432 

in  diseases  of  pancreas,  223,  322 

muscle  fibres  in,  in  diseases  of 

pancreas,  328 
nuclei   in,    in   diseases   of   pan- 
creas, 330 
white  appearance  of,  in  diseases 
of  pancreas,  225 
Ferment,     diastatic,     method     of 
testing  for,  in  diseases  of  pan- 
creas, 267 
emulsif,  119 

fat-splitting,  in  diseases  of  pan- 
creas,   method    of    testing 
for,  266 
in  urine,  in  diagnosis  of  dis- 
eases of  pancreas,  335 
in  diseases  of  pancreas,  263 
milk-curdling,      of      pancreatic 

juice.  III,  128 
proteolytic,   method   of  testing 
for,  in  pancreatic  diseases, 

of  pancreatic  juice,  114 
Ferments  of  pancreatic  jtiice,  in 
Fever  in  diseases  of  pancreas,  313 
Fibres,  muscle,  in  feces,  in  diseases 

of  pancreas,  328 
Fibro-adenoma  of  pancreas,  187 
Fish,  pancreas  of,  20 
Fitz's  rule  in  acitte  pancreatitis, 

399 
Focal  necrosis  of  pancreas,  137 
Frenum  carunculse,  36 


Gall-stones,    acute    pancreatitis 
from,  389 
and    chronic    pancreatitis,    dif- 
ferentiation, 43 1 
pancreatitis  from,  365 
relation  of  chronic  pancreatitis 
to,  154 
Gangrenous  pancreatitis,  147 
Gland,  abdominal  salivary,  71 

salivaire  abdominale,  71 
Glycosuria   after   partial   extirpa- 
tion of  pancreas,  271 
alimentary,  after  partial  extir- 
pation of  pancreas,  271 
from     disturbances    of    pan- 
creas, 304 
in    diagnosis    of    diseases    of 
.pancreas,  337 


Glycosuria,  alimentary,  relation  of 
pancreas  to,   305 

as  symptom  of  diseases  of  pan- 
creas, 333 

association  of,  with  acute  pan- 
creatitis, 288 

in  diseases  of  pancreas,  241 

in  pancreatic  calculi,  480 

transitory,  276 
Gout  in  diabetes,  301 


Hematoma  of  pancreas,  175 
Hemipeptone,  115 
Hemochromatosis,  302 

chronic  interstitial  pancreatitis 
in,  166 
Hemoglobin  in  pancreatitis,  232 
Hemorrhage   in   diseases   of   pan- 
creas, 317 
into       pancreas,       pancreatitis 

from,  368 
of  pancreas,  137 
in  diabetes,  287 
relation    of,    to    acute    pan- 
creatitis, 149 
Hemorrhagic    cysts    of    pancreas, 

509 
pancreatitis,  138,  146,  149 
pancreas  in,  147 
Hernial  sacs,  pancreas  in,  56 
Histology  of  pancreas,  71 
Hyaline    degeneration    in    islands 
of  Langerhans  in  diabetes, 

295 
of  pancreas,  135 
Hydatid  cyst  of  pancreas,  177,  510 


Incisura  pancreatis,  29 

Indicanuria    in    diagnosis    of   dis- 
eases of  pancreas,  336 
in  diseases  of  pancreas,  233 

Induration  of  pancreas  from  for- 
eign substances,  150 

Infantilism,  pancreatic,  131 

Infectious     diseases,     pancreatitis 
in,  159 
nature  of  diabetes,  277 

Infiltration,    fatty,    of    pancreas, 

134 
Inflammatory   affections   of   pan- 
creas; 140,  361 
etiology,  363 
historical  references,  361 
changes   in  pancreas   in  diabe- 
tes, 286 
Influenza,  pancreatitis  and,  160 


Index 


541 


Injuries  of  pancreas,  345 

sequels,  358 
Interacinar  islands,  78 

islets,  pathological   changes  in, 

in  diabetes,  295 
pancreatitis  in  diabetes,  292 
Interstitial    pancreatitis,   chronic, 

in  diabetes,  289 
Intertubular  cell-clumps,  yS. 
Intestine,    effect   on   exclusion   of 

pancreatic  secretion  on,  210 
Islands,  interacinar,  78 
of  Langerhans,  78 

absence  of,  in  diabetes,  297 
atrophy  of,  in  diabetes,  297 
diminished     number     of,     in 

diabetes,  297 
hyaline    degeneration    in,    in 

diabetes,  295 
in     production     of     internal 

secretion  of  pancreas,  292 
position,  87 

size  and  distribution,  87 
swelling  and  increase  in  size 
of,  in  diabetes,  299 
primary,  88 
Islet,  principal,  88 
Islets,     interacinar,     pathological 
changes  in,  in  diabetes,  295 


Jaundice,    black,    in   diseases    of 
pancreas,  320 
in  chronic  pancreatitis,  428 
in  diseases  of  pancreas,  319 


Lacerations  of  pancreas,  346 

symptoms  and  diagnosis,  352 
treatment,  353 
Lactase,  iii,  121 
Langerhans,  islands  of,  78 

absence   of,   in  diabetes,    297 
atrophy  of,  in  diabetes,  297 
diminished     number     of,     in 

diabetes,  297 
hyaline    degeneration    in,    in 

diabetes,  295 
in     production     of     internal 
secretion  of  pancreas,    292 
position,  87 

size  and  distribution,  87 
swelling  and  increase  in  size 
of,  in  diabetes,  299 
Lesser  pancreas,  30 
Leukocytosis  in  diseases  of  pan- 
creas, 232 


Lipuria  in  diagnosis  of  diseases  of 
pancreas,  337 
in  diseases  of  pancreas,  264 
Liver,  cancer  of,  and  chronic  pan- 
creatitis,  differentiation,   431 
cirrhosis  of,  pancreas  in,  165 
Lobules  of  pancreas,  73 
Lymphadenoma  of  pancreas,   188 
Lymphatics  of  pancreas,  34 

Maltase,  112 

Maltosuria  as  symptom  of  diseases 
of  pancreas,  333 
in  diseases  of  pancreas,  241 

Mammalia,  pancreas  of,  22 

Metabolic  symptoms  of  diseases 
of  pancreas,  333 

Milk-curdling  ferment  of  pancrea- 
tic juice,  III,  128 

Milk-tube,  Schmidt-Stokes,  212 

Mumps  and  pancreatitis,  relation 
of,  160,  369 

Muscle  fibres  in  feces  in  diseases 
of  pancreas,  328 

Nausea  and  vomiting  in  diseases 

of  pancreas,  321 
Necrosis,  fat,  in  diagnosis  of  dis- 
eases of  pancreas,  337 
of  pancreas,  190 

and  bacterial  invasion,  195 
experimental       production 
of,  196 
focal,  of  pancreas,  137 
Nerves  of  pancreas,  34 
Nervous  system  in  production  of 

diabetes,  276 
Neuralgia,  celiac,  315 
Nuclei  in  feces  in  diseases  of  pan- 
creas, 330 

Omental  tuberosity  of  pancreas, 

Operation  for  exploring  head  of 
pancreas  and  common  bile-duct, 

458 

Opie's  test  for  fat-splitting  fer- 
ment in  urine  in  diagnosis  of 
diseases  of  pancreas,  335 

Oxaluria  in  diagnosis  of  diseases 
of  pancreas,  337 
in  diseases  of  pancreas,  239 

Pain  and  tenderness  in  diseases 
of  pancreas,  314 


542 


Index 


Pancreas,  abscess  of,  and  suppu- 
rative pancreatitis,  150 
accessorium,  49 
adenoma  of,  187,  525 

diagnosis  and  treatment,  525 
alveoli  of,  76 

amyloid  degeneration  of,  135 
anatomical  anomalies  of,  46 
anatomy  of,  28 

comparative,  17 
apoplectic  cysts  of,  175,  506 
arteries  of,  32,  33 
as  seat  of  secondary  deposits  of 

malignant  growths,  186 
atrophy  of,  129 

cachectic,  130 

in  diabetes,  129,  280 

secondary,  133 
blood  changes  from  diseases  of, 

230 
blood-supply  of,  32 

alterations    in,    as    cause    of 
chronic  interstitial  changes, 
164 
body  of,  28,  30 
bullet  wounds  of,  355 
symptoms,  356 
treatment,  356 
calculi  of,   473.     See  also  Pan- 
creatic calculi. 
cancer  of,  180,  505,  512 

and  chronic  pancreatitis,  dif- 
ferentiation, 340,  429 

differential  diagnosis,  517 

in  diabetes,  283 

secondary,  186 

deposits  from,  184 

symptoms,  514 

treatment,  521 
catarrh  of,  374 
chemical  pathology  of,  206 
cirrhosis  of,  416 
color  of,  28 

comparative  anatomy  of,  17 
congenital  cystic  disease  of,  177, 

509 
connective-tissue     of,     arrange- 
ment, 71 
consistency  of,  28 
cystadenoma  of,  177,  505 
cystic  epithelioma  of,  177,  505 
neoplasms  of,  176 
simple  tumors  of,  505 
cysts  of,  172,  487 

and  trauma,  relation  of,   179 

contents,  500 

diagnosis,  497 

digestive  power  of  fluid,  500 


Pancreas,  cysts  of,  etiology,  488 

in  diabetes,  282 

physical  signs,  492 

shape,  498 

symptoms,  490 

termination,  502 

treatment,  502 
statistics  on,  504 
digestive  functions  of,  97 

symptoms  in,  320 
diseases  of,  126 

acetone  bodies  in  urine  in,  237 

alimentary    glycosuria    from, 

304 
in  diagnosis  of,  337 
alterations  of  appetite  in,  320 
association  of,   with  diseases 

of  biliary  passages,  144 
azotorrhea  in,  328 
azoturia  in,  236 
bile  in  urine  in,  235 
black  jaundice  in,  320 
blood  in  feces  in,  332 
calcium  oxalate  in  urine  in, 

239. 
carbohydrates    in    urine    in, 

240 
chlorides  in  urine  in,  237 
dependence  of  diabetes  upon, 

269 
diabetes  as  symptom  of,  333 
diagnosis,  311 
dyspepsia  in,  320 
emaciation  in,  320 
ethereal  sulphates  in  urine  in, 

233 
fat  in  feces  in,  210,  211 

necrosis  in  diagnosis  of,  337 
fat-splitting       ferment        in, 
method  of  testing  for, 
266 
in  urine  in,  263 

in  diagnosis  of,  335 
fatty  feces  in,  323 
feces  in,  322 
fever  in,  313 
glycosuria    as    symptom    of, 

333 
glycosuria  in,  241 
hemorrhage  in,  317 
increased  flow  of  saliva  in,  33  2 
indicanuria  in,  233 
indicanuria    in    diagnosis   of, 

jaundice  in,  319 
leukocytosis  in,  232 
lipuria  in,  264 
lipuria  in  diagnosis  of,  337 


Index 


543 


Pancreas,  diseases,  maltosuria  as 
symptom,  333 
maltosuria  in,  241 
metabolic  symptoms,  333 
method  of  testing  for  diasta- 
tic  ferment  in,  267 
for    proteolytic    ferment 
in,  265 
muscle  fibres  in  feces  in,  328 
nausea  and  vomiting  in,  321 
nuclei  in  feces  in,  330 
oxaluria  in,  239 
oxaluria  in  diagnosis  of,  337 
pain  and  tenderness  in,  314 
pancreatic   reaction  in  urine 

as  symptom  of,  334 
pentosuria    as    symptom    of, 

333 
pentosuria  in,  241 
phosphaturia  in,  236 
phosphaturia  in  diagnosis  of, 

336 
physical  signs,  312 
pressure  symptoms  in,  316 
relation    of    urobilinuria    to 

bile -pigments  in,  235 
Sahli's  test  in,  338 
steatorrhea  in,  323 
stercobilin  in,  331 
symptomatology,  311 
test  meals  in,  339 
urine  in,  233 
vomiting  in,  321 
white  appearance  of  feces  in, 
225 
di visum,  49 
ducts  of,  ^6 
embryology  of,  41 
extirpation   of,    diabetes    after, 
269,  270 
partial  alimentary  glycosuria 
after,  271 
gl5^cosuria  after,  271 
utilisation  of  proteids   after, 
221 
fat  necrosis  of,  190 

and  bacterial  invasion,  195 
experimental  production  of, 
196 
fatty  degeneration  of,  134 
in  diabetes,  280 
infiltration  of,  134 
feces  in  diseases  of,  223 
fibro-adenoma  of ,  187 
focal  necrosis  of,  137 
head  of,  28,  29 

and  common  bile-duct,  opera- 
tion for  exploring,  458 


Pancreas,  hematoma  of,  175 

hemorrhage  of,  137 
in  diabetes,  287 
pancreatitis  from,  368 
relation  of,  to  acute  pancrea- 
titis, 149 

hemorrhagic  cysts  of,  509 

histology  of,  7 1 

hyaline  degeneration  of,  135 

hydatid  cyst  of,  177,  510 

in  cirrhosis  of  liver,  165 

in  hemorrhagic  pancreatitis,  147 

in  hernial  sacs,  56 

in  syphilis,  161 

induration  of,  from  foreign  sub- 
stances, 150 

inflammatory  affections  of,  140, 
361 
classification,  362 
etiology,  363 
historical  references,  361 
changes  in,  in  diabetes,  286 

injuries  of,  345 
sequels,  358 

internal  secretion  of,  islands 
of  Langerhans  in  production 
of,  292 

lacerations  of,  346 

sj^mptoms  and  diagnosis,  352 
treatment,  353 

lesser,  30 

lobules  of,  73 

lymphadenoma  of,  188 

lymphatics  of,  34 

methods  of  exposing,  69 

minus,  46 

neck  of,  28,  30 

nerves  of,  34 

of  anthropoidea,  26 

of  aquatic  mammals,  24 

of  birds,  22 

of  carnivora,  24 

of  cat,  25 

of  dog,  25 

of  fish,  20 

of  mammalia,  22 

of  reptiles,  21 

of  rodents,  23 

of  ruminants,  24 

omental  tuberosity  of,  32 

parvum,  47 

pathology  of,  126 

penetrating  wounds  of,  357 
treatment,  358 

peritoneum  of,  35 

physiology  of,  96 

position  of,  28 

proliferation  cysts  of,   176,  505 


544 


Index 


Pancreas,  proximity  of,  to  stom- 
ach, 65 
pseudo-cysts  of,  178 
pyemic  abscess  of,  150 
relation  of,  to  alimentary  glyco- 
suria, 305 

to  peritoneum,  68 
retention  cj'-sts  of,  175 
retroperitoneal  position  of,  68 
sarcocarcinoma  of,  185 
sarcoma  of,  185,  523 

secondary,  186 
shape  of,  28 
size  of,  28 
structure  of,  71 
suppurative  catarrh  of,  378 
surgical  anatomy  of,  64 
syphilis  of,  526 

treatment,  527 
tail  of,  29,  30,  32 
triangle  of  infection  of,  152 
tuberculosis  of,  163,  525 

symptoms  and  diagnosis,  526 

treatment,  526 
tumors  of,  179,  512 

diagnosis   and   symptoms   of, 
312 
uncinate  process  of,  29 
veins  of,  32,  33,  34 
wounds  of,  345 
Pancreatic  acne,  175 
apoplexy,  138 
calculi,  169,  473 

composition  of,  475 

glycosuria  in,  480 

in  diabetes,  281 

symptoms  of,  479 

treatment  of,  482 
casein,  128 
diastase,  11 i 
duct,  accessory,  44 
ducts,  anatomical  variations  of, 

enzymes,  detection  of,  264 
extracts  in  diabetes,  306 
infantilism,  131 
juice,  digestion  of  fat  by,  117 
digestive    disturbances    from 
absence  or  diminution  of, 
208 
enzymes  of,  1 1 1 
effect  of    exclusion    of,  from 
intestine,  210 
on  proteid,  114 
excessive,  207 
external,     composition     and 

characters,  106 
ferments  of,  1 1 1 


Pancreatic    juice,    mechanism    of 
flow,  98 
milk-curdling  ferment  of,  128 
proteolytic  ferment  of,  114 
reduction    or    failure    of,    as 
cause  of  impaired  digestion 
of  starchy  foods,  223 
steapsin  of,  118 
total  daily  output,  108 
ranula,  175,  498 
reaction,  243 

in  urine  as  symptom  of  dis- 
eases of  pancreas,  334 
sialorrhea,  332 
Pancreatitis,  acute,  384 

association  of  glycosuria  with, 

288 
diagnosis  of,  398,  406 
etiolog}^  of,  387 
Fitz's  rule  in,  399 
gall-stones  as  cause  of,  389 
in  diabetes,  287 
relation  of  pancreatic  hemor- 
rhage to,  149 
symptoms  of,  384 
treatment  of,  400 
and  influenza,  160 
and  typhoid  fever,  159 
chronic,  412 

and  cancer  of  liver,  differen- 
tiation, 431 
of     pancreas,      differentia- 
tion, 340,  429 
and    gall-stones,     differentia- 
tion, 431 
bacteria  as  cause  of,  151 
diagnosis,  differential,  429 
dyspeptic     disturbances     in, 

428 
etiology  of,  412 
feces  in,  432 

from  extension  of  inflamma- 
tory   process    from    neigh- 
boring organs,  166 
interacinar  form,  416 
interlobular  form,  416 
interstitial,  in  diabetes,  289 
in  hemochromatosis,  166 
interacinar  type,  169 
interlobular  type,  167 
jaundice  in,  428 
pain  and  tenderness  in,  427 
prognosis  of,  433 
relation  of,   to   cholelithiasis, 

154 
alcohol  to,  424 
symptoms  of,  426 
treatment  of,  433 


Index 


545 


Pancreatitis, chronic,  treatment  of, 
surgical,  435 
results  from,  468 
urine  in,  428 
erythrocytes  in,  231 
from  hemorrhage  into  pancreas, 

368 
gall-stones  as  cause,  365 
gangrenous,  147 
hemoglobin  in,  232 
hemorrhagic,  138,  146,  149 

pancreas  in,  147 
in  infectious  diseases,  159 
influence  of  alcohol  on  produc- 
tion of,  160 
interacinar,  in  diabetes,  292 
mumps  and,  160 
relation  of,  369 
subacute,  404 

treatment  of,  407 
suppurative,  147 

and  abscess  of  pancreas,  150 
syphilitic,  161 
Pancreolithic  catarrh,  473 
Pancreolithotomy,  485 
Pancreon,  218 
Papilla  major,  36 

minor,  39 
Paranuclein,  237 

Parotitis   and   pancreatitis,    rela- 
tion of,  160,  369 
Pathology,  chemical,  of  pancreas, 
206 
of  pancreas,  126 
Penetrating  wounds  of  pancreas, 

357 
treatment,  358 
Pentosuria    as    symptom    of    dis- 
eases of  pancreas,  333 
in  diseases  of  pancreas,  241 
Peritoneum  of  pancreas,  35 

relations  of  pancreas  to,  68 
Phosphaturia  in  diagnosis  of  dis- 
eases of  pancreas,  336 
in  diseases  of  pancreas,  236 
Physiology  of  pancreas,  96 
Pialyn,  in 
Plasmosomes,  78 
Plexus,  solar,  disease  of,  as  cause 

of  diabetes,  272 
Plica  longitudinalis,  36 
Polypeptides,  115 
Pressure  symptoms  in  diseases  of 

pancreas,  336 
Primary  islands,  88 
Principal  islet,  88 
Proliferation    cysts    of    pancreas, 
176-  505 
35 


Prosecretin,  104 

Proteids,  effect  of  pancreatic  juice 
on,  114 
utilisation  of,  after  extirpation 
of  pancreas,  221 
Proteolytic    ferment,    method    of 
testing    for,    in    pancreatic 
diseases,  265 
of  pancreatic  juice,  114 
Pseudo-cysts  of  pancreas,  178 
Pyemic  abscess  of  pancreas,^! 50 

Ranula  pancreatica,  175,  498 
Reptiles,  pancreas  of,  2 1 
Retention  cysts  of  pancreas,  175 
Rodents,  pancreas  of,  23 
Ruminants,  pancreas  of,  24 


Sahli's  test  in  diseases  of  pan- 
creas, 338 

Saliva,  increased  flow  of,  in  dis- 
eases of  pancreas,  332 

Salivary  gland,  abdominal,  71 

Santorini,  duct  of,  38,  44 

Sapocrinin,  105 

Sarcocarcinoma  of  pancreas,    185 

Sarcoma  of  pancreas,  185,  523 
secondary,  of  pancreas,  186 

Saviotti's  canals,  74 

Schmidt-Stokes  milk-tube,  212 

Secretin,  103 
in  diabetes,  306 

Sialorrhoea  pancreatica,  332 

Sinusoids,  81 

Solar  plexus,  disease  of,  as  cause 
of  diabetes,  272 

Starchy  foods,  impaired  digestion 
of,  reduction  or  failure  of  pan- 
creatic secretion  as  cause,  223 

Steapsin,  in 

of  pancreatic  juice,  118 

Steatorrhea  in  diseases  of  pan- 
creas, 323 

Stercobilin  in  diseases  of  pancreas, 

331  .     .  , 

Stomach,    proximity   of   pancreas 

to,  65 
Structure  of  pancreas,  71 
Svilphates,    ethereal,   in   urine,   in 

diseases  of  pancreas,  233 
Suppurative  catarrh  of  pancreas, 

378       .  . 
pancreatitis,  147 

and  abscess  of  pancreas,  150 
Surgical  anatomy  of  pancreas,  64 
Swordfish,  pancreas  of,  20 


546 


Index 


Symptoms,  general,  of  diseases  of 

pancreas,  311 
Syphilis  in  diabetes,  301 

of  pancreas,  526 
treatment,  527 

pancreas  in,  161 
Syphilitic  pancreatitis,  161 


Tenderness  and  pain  in  diseases 

of  pancreas,  314 
Test  meals  in  diseases  of  pancreas, 

339. 
Transitory  glycosuria,  276 
Trauma,   cysts   of  pancreas  and, 

relation  of,  179 
Triangle  of  infection  of  pancreas, 

152. 
Trypsin,  in,  113 
Tuberculosis  of  pancreas,  163,  525 
symptoms  and  diagnosis,  526 
treatment,  526 
Tumors,  cystic,  of  pancreas,  176 
simple,  of  pancreas,  505 
of  pancreas,  179,  512 

diagnosis  and   symptoms   of, 
312 
Typhoid   fever,   pancreatitis   and, 
159 


Uncinate  process  of  pancreas,  29 
Urine,   acetone  bodies  in,  in  dis- 
eases of  pancreas,  237 
bile  in,  in  diseases  of  pancreas, 
23s 


Urine,  calcium  oxalate  in,  in  dis- 
eases of  pancreas,  239 
carbohydrates  in,  in  diseases'of 

pancreas,  240 
ethereal  svilphates  in,  in  diseases 

of  pancreas,  233 
fat-splitting  ferment  in,  in  diag- 
nosis of  diseases  of  pan- 
creas, 335 
in     diseases     of     pancreas, 
263 
in  chronic  pancreatitis,  428 
in  diseases  of  pancreas,  233 
pancreatic  reaction  in,  243 

as  symptom  of  diseases  of 
pancreas,  334 
Urobilinuria,  relation  of,  to  bile- 
pigments,    in   diseases    of   pan- 
creas, 235 


Vater,  ampulla  of,  37,  39 
mode  of  formation,  59 
Veins  of  pancreas,  32,  33,  34 
Vomiting  and  nausea  in  diseases 
of  pancreas,  321 


White  appearance  of  feces  in  dis- 
eases of  pancreas,  225 
Wirsung,  duct  of,  36,  44 
Wounds,  bullet,  of  pancreas,  355  j 
symptoms,  356 
treatment,  356 
of  pancreas,  345 
penetrating,  of  pancreas,  357 
treatment,  358 


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PATHOLOGY. 


Wells*  Chemical  Pathology 

Chemical  Pathology.  Ik^ng  a  Discussion  of  General  Pathology 
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American  Medicine 

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Dtirck  and  Hektoen*s 

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HowelFs  Physiology 


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write  a  text-book  on  this  subject.  Main  emphasis  has  been  laid  upon  those  facts 
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PATHOLOGY. 


Stengel's 
Text-Book  of  Pathology 

Just  Issued— The  New  ^5th)  Edition 


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dealing  with  General  Pathology  has  been  most  extensively  revised,  several  of  the 
important  chapters  having  been  practically  rewritten.  A  very  useful  addition 
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most  important  methods  at  present  in  use  for  the  study  of  patholog5^  including, 
however,  only  those  methods  capable  of  giving  satisfactory  results.  The  book 
will  be  found  to  maintain  fully  its  popularity. 


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William  H.  Welch,  M.  D.. 

Professor  of  Pathology,  Johns  Hopkins  University,  Baltimore,  Md. 

"  I  consider  the  work  abreast  of  modern  pathology,  and  useful  to  both  students  and  practi- 
tioners. It  presents  in  a  concise  and  well-considered  form  the  essential  facts  of  general  and 
special  pathologic  anatomy,  with  more  than  usual  emphasis  upon  pathologic  physiology." 

Ludvig  Hektoen,  M.  D., 

Professor  of  Pathology,  Rush  Medical  College,  Chicago. 

"  I  regard  it  as  the  most  serviceable  text-book  for  students  on  this  subject  yet  written  by  an 
American  author." 

The  Lancet,  London 

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sible, and  more  especially  from  the  point  of  view  of  the  'clinical  pathologist.'  These  subjects 
have  been  faithfully  carried  out,  and  a  valuable  text-book  is  the  result.  We  can  most  favorably 
recommend  it  to  our  readers  as  a  thoroughly  practical  work  on  clinical  pathology." 


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Professor  of  Gynecology,  Johns  Hopkins  University ,  Baltimore. 

"  Dr.  Borland's  dictionary  is  admirable.     It  is  so  well  gotten  up  and  of  such  convenient 
siee.     No  errors  have  been  found  in  my  use  of  it." 

J.  Collins  Warren.  M.D..  LL.D.,  F.R.C.S.  (Hon.) 

Professor  of.  Surgt-}y,  Harvard  Medical  School. 

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KMnRYOLOCY. 


Heisler's 
Text-Book  qf  Embryology 

Just  Issued — The  New  fsdj  Edition 


A  Text=Book  of  Embryology,  By  John  C.  Heisler,  M.D.,  Pro- 
fessor of  Anatomy  in  the  Medico-Chirurf^ical  College,  Philadelphia. 
Octavo  volume  of  435  pages,  with  212  illustrations,  32  of  them  in 
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WITH    212     ILLUSTRATIONS,     32     IN     COLORS 

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yet  sufficiently  full  text-book  upon  the  subject  be  available.  This  new  edition 
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Many  portions  have  been  entirely  rewritten,  and  a  great  deal  of  new  and  impor- 
tant matter  added.  A  number  of  new  illustrations  have  also  been  introduced  and 
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already  won.      Heisler' s  Embryology  has  become  a  standard  work. 


PERSONAL  AND   PRESS  OPINIONS 


G.  Carl  Huber.  M.  D., 

Professor  of  Histology  and  Embryology,  University  of  Michigan,  Ann  Arbor. 
"  I  find  the   second  edition   of  '  A  Text-Book  of  Embryology'  by  Dr.  Heisler  an  improve- 
ment on  the  first.     The   figures   added   increase   greatly  the  value  of  the  work.     I  am  again 
recommending  it  to  our  students." 

William  Wathen.  M.  D.. 

Professor  of  Obstetrics,  Abdominal  Surgery,  and  Gynecology,  and  Dean,  Kentucky  School  of 

Medicine,  Louisville ,  Ky. 
"  It  is  systematic,  scientific,  full  of  simplicity,  and  just  such  a  work  as  a  medical  student 
will  be  able  to  comprehend." 

Birmingham  Medical  Review,  England 

"  We  can  most  confidently  recommend  Dr.  Heisler's  book  to  the  student  of  biology  or 
medicine  for  his  careful  study,  if  his  aim  be  to  acquire  a  sound  and  practical  acquaintance  with 
the  subject  of  embryology." 


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Mallory  and  Wright's 
Pathologic  Technique 

Recently  Issued— Third  Edition,  Revised  and  Enlar£>ed 


Pathologic  Technique.  A  Practical  Manual  for  Workers  in  Patho- 
logic Histology,  including  Directions  for  the  Performance  of  Autopsies 
and  for  Clinical  Diagnosis  by  Laboratory  Methods.  By  Frank  B. 
Mallory,  M.  D.,  Associate  Professor  of  Pathology,  Harvard  Univer- 
sity ;  and  James  H.  Wright,  M.  D.,  Director  of  the  Clinico-Pathologic 
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with  138  illustrations.      Cloth,  ^3.00  net. 

WITH  CHAPTERS  ON  POST-MORTEM  TECHNIQUE  AND  AUTOPSIES 

In  revising  the  book  for  the  new  edition  the  authors  have  kept  in  view  the 
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for  the  cultivation  of  Anaerobic  Bacteria.  There  have  also  been  added  new 
staining  methods  for  elastic  tissue  by  Weigert,  for  bone  by  Schmorl,  and  for  con- 
nective tissue  by  Mallory.  The  new  edition  of  this  valuable  work  keeps  pace 
with  the  great  advances  made  in  pathology,  and  will  continue  to  be  a  most  useful 
laboratory  and  post-mortem  guide,  full  of  practical  information. 


PERSONAL  AND   PRESS  OPINIONS 


Wm.  H.  Welch.  M.  D., 

Professor  of  Pathology,  Johns  Hopkins  University ,  Baltimore. 

"  I  have  been  looking  forward  to  the  pubHcation  of  this  book,  and  I  am  glad  to  say  that  I 
find  it  a  most  useful  laboratory  and  post-mortem  guide,  full  of  practical  information  and  well 
up  to  date." 

Boston  Medical  and  Surgical  Journal 

"  This  manual,  since  its  first  appearance,  has  been  recognized  as  the  standard  guide  in  patho- 
logical technique,  and  has  become  well-nigh  indispensable  to  the  laboratory  worker." 

journal  of  the  American  Medical  Association 

"  One  of  the  most  complete  works  on  the  subject,  and  one  which  should  be  in  the  library 
of  every  physician  who  hopes  to  keep  pace  with  the  great  advances  made  in  pathology." 


HISTOLOGY. 


Bohm,  Davidoff,  anb 
Huber's  Histology 


A  Text=Book  of  Human  Histology.  Including  Microscopic  Tech- 
nic.  By  Dr.  A.  A.  Bohm  and  Dr.  M.  von  Davidoff,  of  Munich,  and 
G.  Garl  Huber,  M.  D.,  Professor  of  Histology  and  Embryology  in 
the  University  of  Michigan,  Ann  Arbor.  Handsome  octavo  of  528 
pages,  with  361  beautiful  original  illustrations.    Flexible  cloth,  ^3.50  net. 

RECENTLY  ISSUED-NEW  (2d)  EDITION,  ENLARGED 

The  work  of  Drs.  Bohm  and  Davidoff  is  well  known  in  the  German  edition, 
and  has  been  considered  one  of  the  most  practically  useful  books  on  the  subject 
of  Human  Histology.  This  second  edition  has  been  in  great  part  rewritten  and 
very  much  enlarged  by  Dr.  Huber,  who  has  also  added  over  one  hundred  origi- 
nal illustrations.  Dr.  Huber' s  extensive  additions  have  rendered  the  work  the 
most  complete  students'  te.xt-book  on  Histology  in  existence. 

Boston  Medical  and  Surgical  Journal 

"  Is  unquestionably  a  text-book  of  tlie  first  rank,  having  been  carefully  written  by  thorough 
masters  of  the  subject,  and  in  certain  directions  it  is  much  superior  to  any  other  histological 
manual." 


DrewV 

Invertebrate  Zoolo^ 

A  Laboratory  Manual  of  Invertebrate  Zoology.  By  Oilman  A. 
Drew,  Ph.D.,  Professor  of  Biology  at  the  University  of  Maine.  With  the 
aid  of  Members  of  the  Zoological  Staff  of  Instructors  of  the  Marine  Biolog- 
ical Laboratory,  Woods  Holl,  Mass.      i2mo  of  200  pages.     Cloth,  ^1.25  net. 

JUST   READY 

The  author  has  had  extensive  experience  in  the  classroom  and  the  laboratory, 
being  in  charge  of  the  Marine  Biological  Laboralorv  at  Woods  Holl,  Massachusetts.  This 
training  has  fitted  him  most  admirably  to  write  such  a  book  as  this.  The  subject  is  pre- 
sented in  a  logical  way,  and  the  type  study  has  been  following,  as  this  method  has  been 
the  prevailing  one  for  many  years. 


SAUNDERS'    BOOKS    ON 


McFarland's 
Pathogenic  Bacteria 

The  New  (5th)  Edition,  Revised 


A  Text=Book  Upon  the  Pathogenic  Bacteria.  By  Joseph  McFar- 
LAND,  M.  D.,  Professor  of  Pathology  and  Bacteriology  in  the  Medico- 
Chirurgical  College  of  Philadelphia,  Pathologist  to  the  Medico-Chirur- 
gical  Hospital,  Philadelphia,  etc.  Octavo  volume  olf  647  pages,  finely 
illustrated.     Cloth,  1^3.50  net. 

JUST  ISSUED 

This  book  gives  a  concise  account  of  the  technical  procedures  necessary  in  the 
study  of  bacteriology,  a  brief  description  of  the  life-history  of  the  important  patho- 
genic bacteria,  and  sufficient  description  of  the  pathologic  lesions  accompanying 
the  micro-organismal  invasions  to  give  an  idea  of  the  origin  of  symptoms  and  the 
causes  of  death.  The  illustrations  are  mainly  reproductions  of  tl  e  best  the  world 
affords,  and  are  beautifully  executed.  In  this  edition  the  entire  work  has  been 
practically  rewritten,  old  matter  eliminated,  and  much  new  matter  inserted. 

H.  B.  Anderson,  M.  D., 

Professor  of  Pathology  and  Bacteriology,   Trinity  Medical  College,  Torotito. 
"  The  book  is  a  satisfactory  one,  and  I  shall  take  pleasure  in  recommending  it  to  the  students 
of  Trinity  College." 

The  Lancet,  London 

"  It  is  excellently  adapted  for  the  medical  students  and  practitioners  for  whom  it  is  avowedly 
written.  .  .  .  The  descriptions  given  are  accurate  and  readable." 


HilFs  Histology  and  Organography 

A  Manual  of  Histology  and  Organography.  By  Charles  Hill, 
M.  D.,  Professor  of  Histology  and  Embryology,  Northwestern  Univer- 
sity, Chicago.  i2mo  of  463  pages,  313  illustrations.  Flexible  leather, 
^2.00  net. 

RECENTLY  ISSUED 

Dr.  Hill's  fifteen  years'  experience  as  a  teacher  of  histology  has  enabled  him  to 
present  a  work  characterized  by  clearness  and  brevity  of  style  and  a  completeness 
of  discussion  rarely  met  in  a  book  of  its  pretensions.  Particular  consideration  is 
given  the  mouth  and  teeth  ;  and  illustrations  are  most  freely  used. 


BA  CFERIOLOG  Y  AND  FA  THOLOG  Y. 


Eyre*s 
Bacteriologic  Technique 


The  Elements  of  Bacteriologic  Technique.  A  Laboratory  Guide 
for  the  Medical,  Dental,  and  Technical  Student.  By  J.  W.  H.  Eyre, 
M.  D.,  F.  R.  S.  Edin.,  Bacteriologist  to  Guy's  Hospital,  London,  and 
Lecturer  on  Bacteriology  at  the  Medical  and  Dental  Schools,  etc. 
Octavo  volume  of  375  pages,  with  170  illustrations.     Cloth,  ;^2.50  net. 

FOR   MEDICAL.  DENTAL.  AND   TECHNICAL   STUDENTS 

This  book  presents,  concisely  yet  clearly,  the  various  methods  at  present  in 
use  for  the  study  of  bacteria,  and  elucidates  such  points  in  their  life-histories  as 
are  debatable  or  still  undetermined.  It  includes  only  those  methods  that  are 
capable  of  giving  satisfactory  results  even  in  the  hands  of  beginners.  The  illus- 
trations are  numerous  and  practical.  The  work  is  designed  with  the  needs  of  the 
technical  student  generally  constantly  in  view. 

The  Lancet,  London 

"  Stamped  throughout  with  evidence  that  the  writer  is  a  practical  teacher,  and  the  directions 
are  more  clearly  given  .   .  .   than  in  any  previous  work." 

Warren's 

Pathology  and   Therapeutics 

Surgical  Pathology  and  Therapeutics.  By  John  Collins  Warren, 
M.  D.,  LL.D.,  F.  R.  C.  S.  (Hon.),  Professor  of  Surgery,  Harvard  Medical 
School.  Octavo,  873  pages,  136  relief  and  lithographic  illustrations,  33 
in  colors.  With  an  Appendix  on  Scientific  Aids  to  Surgical  Diagnosis 
and  a  series  of  articles  on  Regional  Bacteriology.  Cloth,  $5.00  net; 
Sheep  or  Half  Morocco,  $6.50  net. 

SECOND    EDITION.  WITH   AN   APPENDIX 

In  the  second  edition  of  this  book  all  the  important  changes  have  been  em- 
bodied in  a  new  Appendix.  In  addition  to  an  enumeration  of  the  scientific  aids  to 
surgical  diagnosis  there  is  presented  a  series  of  sections  on  regional  bacteriology, 
in  which  are  given  a  description  of  the  flora  of  the  affected  part,  and  the  general 
principles  of  treating  the  affections  they  produce. 

Roswell   Park.  M.  D., 

In  the  Harvard  Graduate  Magazine. 

"  I  think  it  is  the  most  creditable  book  on  surgical  pathology,  and  the  most  beautiful  medica! 
illustration  of  the  bookmakers'  art  that  has  ever  been  issued  from  the  American  press. 


SAUNDERS'    BOOKS   ON 


Dtirck  and  Hektoen's 

Special    P&tholo^ic   Histolog'y 


Atlas  and  Epitome  of  Special  Pathologic  Histology.     By  Dr.  H. 

DiJRCK,  of  Munich.  Edited,  with  additions,  by  Ludvig  Hektoen,  M.  D., 
Professor  of  Pathology,  Rush  Medical  College,  Chicago.  In  two  parts. 
Part  I. — Circulatory,  Respiratory,  and  Gastro-intestinal  Tracts.  120 
colored  figures  on  62  plates,  and  158  pages  of  text.  Part  II. — Liver, 
Urinary  and  Sexual  Organs,  Nervous  System,  Skin,  Muscles,  and 
Bones.  123  colored  figures  on  60  plates,  and  192  pages  of  text.  Per 
part :  Cloth,  ;^3.oo  net.     In  Saunders'  Hand-Atlas  Series. 

The  great  value  of  these  plates  is  that  they  represent  in  the  exact  colors  the  effect 
of  the  stains,  which  is  of  such  great  importance  for  the  differentiation  of  tissue. 
The  text  portion  of  the  book  is  admirable,  and,  while  brief,  it  is  entirely  satisfac- 
tory in  that  the  leading  facts  are  stated,  and  so  stated  that  the  reader  feels  he  has 
grasped  the  subject  extensively. 

William  H.  Welch,  M.  D.. 

Professor  of  Pathology,  Johns  Hopkins  University,  Baltimore. 

"  I  consider  Diirck's  'Atlas  of  Special  Pathologic  Histology,'  edited  by  Hektoen,  a  very 
useful  book  for  students  and  others.     The  plates  are  admirable." 

Sobotta  and  Huber*s 
Human  Histolo^ 

Atlas  and  Epitome  of  Human  Histology.  By  Privatdocent  Dr. 
J.  Sobotta,  of  Wiirzburg.  Edited,  with  additions,  by  G.  Carl  Huber, 
M.  D.,  Professor  of  Histology  and  Embryology  in  the  University  of 
Michigan,  Ann  Arbor.  With  214  colored  figures  on  80  plates,  68 
text-illustrations,  and  248  pages  of  text.  Cloth,  ^^4.50  net.  /« 
Saunders'  Ha?id- Atlas  Series. 

INCLUDING   MICROSCOPIC   ANATOMY 

The  work  combines  an  abundance  of  well-chosen  and  most  accurate  illustra- 
tions, with  a  concise  text,  and  in  such  a  manner  as  to  make  it  both  atlas  and  text- 
book. The  great  majority  of  the  illustrations  were  made  from  sections  prepared 
from  human  tissues,  and  always  from  fresh  and  in  every  respect  normal  specimens. 
The  colored  lithographic  plates  have  been  produced  with  the  aid  of  over  thirty  colors. 

Boston  Medical  and  Surgical  Journal 

"  In  color  and  proportion  they  are  characterized  by  gratifying  accuracy  and  lithographic 
beauty." 


PHYSIOLOGY.  13 


American  Text-  Book  of  Physiology 


American  Text=Book  of  Physiology.  In  two  volumes.  Edited  by 
William  H.  Howell,  Ph.D.,  M.  D.,  Professor  of  Physiology  in  the 
Johns  Hopkins  University,  Baltimore,  Md.  Two  royal  octavo  volumes 
of  about  600  pages  each,  fully  illustrated.  Per  volume  :  Cloth,  $i.QO 
net;  Sheep  or  Half  Morocco,  $4.25  net. 

SECOND    EDITION,   REVISED    AND    ENLARGED 

Even  in  the  short  time  that  has  elapsed  since  the  first  edition  of  this  work 
there  has  been  much  progress  in  Physiology,  and  in  this  edition  the  book  has  been 
thoroughly  revised  to  keep  pace  with  this  progress.  The  chapter  upon  the  Cen- 
tral Nervous  System  has  been  entirely  rewritten.  A  section  on  Physical  Chem- 
istry forms  a  valuable  addition,  since  these  views  are  taking  a  large  part  in  current 
discussion  in  physiologic  and  medical  literature. 

The  Madical  News 

"  The  work  will  stand  as  a  work  of  reference  on  physiology.  To  him  who  desires  to  know 
the  status  of  modern  physiology,  who  expects  to  obtain  suggestions  as  to  further  physiologic 
inquiry,  we  know  of  none  in  English  which  so  eminently  meets  such  a  demand." 

Stewart's  Physiology 

A  Manual  of  Physiology,  with  Practical  Exercises.  For  Students 
and  Practitioners.  By  G.  N.  Stewart,  M.  A.,  M.  D.,  D.  Sc,  Professor 
of  Physiology  in  the  University  of  Chicago,  Chicago.  Octavo 
volume  of  911    pages,  with   395   text-illustrations   and  colored  plates. 

Cloth,  ^4.00  net. 

RECENTLY  ISSUED— NEW  (5th)  EDITION 


This  work  is  written  in  a  plain  and  attractive  style  that  renders  it  particularly 
suited  to  the  needs  of  students.  The  systematic  portion  is  so  treated  that  it  can 
be  used  independently  of  the  practical  exercises.  In  the  present  edition  a  con- 
siderable amount  of  new  matter  has  been  added,  especially  to  the  chapters  on 
Blood,  Digestion,  and  the  Central  Nervous  System. 

Philadelphia  Medical  Journal 

"  Those  familiar  with  the  attainments  of  Prof.  Stewart  as  an  original  investigator,  as  a 
teacher  and  a  writer,  need  no  assurance  that  in  this  volume  he  has  presented  in  a  terse,  concise, 
accurate  manner  the  essential  and  best  established  facts  of  physiology  in  a  most  attractive 
manner." 


14  SAUNDERS'   BOOKS   ON 

Levy  and  Klemperer's 
Clinical  Bacteriology 

The  Elements  of  Clinical  Bacteriology.  By  Drs.  Ernst  Levy  and 
Felix  Klemperer,  of  the  University  of  Strasburg.  Translated  and 
edited  by  Augustus  A.  Eshner,  M.  D.,  Professor  of  Clinical  Medicine, 
Philadelphia  Polyclinic.  Octavo  volume  of  440  pages,  fully  illustrated. 
Cloth,  ^2.50  net. 

S.  Solis-Cohen,  M.  D., 

Professor  of  Clinical  Medicine,  Jefferso7t  Medical  College,  Philadelphia. 

"  1  consider  it  an  excellent  book.     I  have  recommended  it  in  speaking  to  my  students." 

Lehmann,  Neumann,  and 
Weaver's  Bacteriology 

Atlas  and  Epitome  of  Bacteriology :  including  a  Text-Book  of 
Special  Bacteriologic  Diagnosis.  By  Prof.  Dr.  K.  B.  Lehmann 
and  Dr.  R.  O.  Neumann,  of  Wiirzburg.  Front  the  Second  Revised  and 
Enlarged  German  Edition.  Edited,  with  additions,  by  G.  H.  Weaver, 
M.  D.,  Assistant  Professor  of  Pathology  and  Bacteriology,  Rush  Medical 
College,  Chicago.  In  two  parts.  Part  I. — 632  colored  figures  on  69 
lithographic  plates.  Part  II. — 511  pages  of  text,  illustrated.  Per  part: 
Cloth,  ^2.50  net.     In  Saunders'  Hand-Atlas  Series. 

Lewis'  Anatomy  and  Physi- 
ology for  Nurses 

Anatomy  and  Physiology  for  Nurses.  By  LeRoy  Lewis,  M.D., 
Surgeon  to  and  Lecturer  on  Anatomy  and  Physiology  for  Nurses  at 
the  Lewis  Hospital,  Bay  City,  Michigan.  i2mo  of  317  pages,  with 
146  illustrations.     Cloth,  $1.^]^  net. 

JUST  ISSUED 

Nurses  Journal  of  the  Pacific  Coast 

"  It  is  not  in  any  sense  rudimentary,  but  comprehensive  in  its  treatment  of  the  subjects  in 
hand." 


PATHOLOGY,   BACTERIOLOGY,   AND    PHYSIOLOGY.  15 

Senn'S    Tumors  second  RevUed  Exlhion 

Pathology  and  Surgical  Treatment  of  Tumors.       By  Nicholas 
Senn,  M.  D.,  Ph.  D.,  LL.D.,  Professor  of  Surgery,  Rush  Medical  Col 
lege,   Chicago.      Handsome  octavo,    718  pages,    with   478    engravings, 
including  12  full-page  colored  plates.     Cloth,  $5.00  net;  Sheep  or  Half 
Morocco,  ^6.50  net. 

"The  most  exhaustive  of  any  recent  book  in  English  on  this  subject.  It  is  well  illus- 
trated, and  will  doubtless  remain  as  the  principal  monograph  on  the  subject  in  our 
language  for  some  years." — Journal  of  the  Atnerican  Medical  Association. 

Stoney's  Bacteriology  and  Technic  ^T^^.'^^, 

BACrRRlOLOGY  AND  SURGICAL  TeCHNIC  FOR  NURSES.       Rv  EmILY  M.  A. 

Stoney,  Superintendent,  Carney  Hospital,  Mass.  Revised  by  Frederic 
R.  Griffith,  M.D.,  Surgeon,  N.  Y.  i2mo  of  278  pages,  illustrated. 
$1.50  net. 

"These  subjects  are  treated  most  accurately  and  up  to  date,  without  the  superfluous 
reading  which  is  so  often  employed.  .  .  .  Nurses  will  find  this  book  of  the  greatest  value." 
—  The  Trained  Nurse  and  Hospital  Review. 

Clarkson's  Histolo^ 

A  Text-Book  of  Histology.  Descriptive  and  Practical.  For  the 
Use  of  Students.  By  Arthur  Clarkson,  M.  B.,  C.  M.  Edin.,  formerly 
Demonstrator  of  Physiology  in  the  Owen's  College,  Manchester,  Eng- 
land. Octavo,  554  pages,  with  174  colored  original  illustrations. 
Cloth,  ^4  00  net. 

"  The  volume  in  the  hands  of  students  will  greatly  aid  in  the  comprehension  of  a  sub- 
ject which  in  most  instances  is  found  rather  difficult.  .  .  .  The  work  must  be  considered 
a  valuable  addition  to  the  list  of  available  text-books,  and  is  to  be  highly  recommended.'" 
. — New  York  Medical  Journal. 

Gorhatn's  Bacteriology 

A  Laboratory  Course  in  Bacteriology.  For  the  Use  of  Medical, 
Agricultural,  and  Industrial  Students.  By  Frederic  P.  Gorham,  A.  M., 
Associate  Professor  of  Biology  in  Brown  University,  Providence,  R.  I., 
etc.      i2mo  of  192  pages,  with  97  illustrations.      Cloth,  ^1.25  net. 

"  One  of  the  best  students'  laboratory  guides  to  the  study  of  bacteriology  on  the  mar- 
ket. .  .  .  The  technic  is  thoroughly  modern  and  amply  sufficient  for  all  practical  pur- 
poses. " — American  Journal  of  the  Medical  Sciences, 

Raymond's  Physiology  NeTsSfSn 

Human  Physiology.  By  Joseph  H.  Raymond,  A.  M.,  M.  D.,  Pro- 
fessor of  Physiology  and  Hygiene,  Long  Island  College  Hospital,  New 
York.     Octavo  of  685  pages,  with  444  illustrations.     Cloth,  I3.50  net. 

"  The  book  is  well  gotten  up  and  well  printed,  and  may  be  regarded  as  a  trustworthy 
guide  for  the  student  and  a  useful  work  of  reference  for  the  genera;  practitioner.  The 
illustrations  are  numerous  and  are  well  executed." — The  Lancet,  London. 


i6  BACTERIOLOGY,   PHYSIOLOGY,  AND  HISTOLOGY. 

Ball's    Bacteriolo^  Recently  Issued— Fifth  Edition,  Revised 

Essentials  of  Bacteriology  :  being  a  concise  and  systematic  intro- 
duction to  the  Study  of  Micro  organisms.  By  M.  \'.  Ball,  M.  D.,  Late 
Bacteriologist  to  St.  Agnes'  Hospital,  Philadelphia.  i2mo  of  236  pages, 
with  96  illustrations,  some  in  colors,  and  5  plates.  Cloth,  |i.oo  net.  In 
Saunders"  Question-  Compend  Series. 

"  The  technic  with  regard  to  media,  staining,  mounting,  and  the  hke  is  culled  from  the 
latest  authoritative  works." — The  Medical  Times,  New  York. 

Budgett's  Physiology  NeT(2d)'E;diS?n 

Essentials  of  Physiology.  Prepared  especially  for  Students  of  Medi- 
cine, and  arranged  with  questions  following  each  chapter.  By  Sidney 
P.  BuDGETT,  M.  D.,  Professor  of  Physiology,  Medical  Department  of 
Washington  University,  St.  Louis.  i6mo  volume  of  233  pages,  finely 
illustrated  with  many  full-page  half-tones.  Cloth,  ^i.oo  net.  In 
Saunders'  Question- Compend  Series. 

"He  has  an  excellent  conception  of  his  subject.  .    .  It   is   one  of   the  most  satisfactory 
books  of  this  class" — University  of  Pennsylvania  Medical  Bulletin. 
V  •      »»•    J     «      .  Recently  Issued 

Leroy  s  Histology  New  od)  Edition 

Essentials  of  Histology.     By  Louis  Leroy,  M.  D.,  Professor  of 

Histology  and  Pathology,  Vanderbilt  University,  Nashville,  Tennessee. 

i2mo,  263  pages,  with  92  original  illustrations.     Cloth,  ^i.oo  net.     In 

Saunders'  Question-  Compend  Series. 

"  The  work  in  its  present  form  stands  as  a  model  of  what  a  student's  aid  should  be  ;  and 
we  unhesitatingly  say  that  the  practitioner  as  well  would  find  a  glance  through  the  book 
of  lasting  benefit." — Tke  Medical  World,  Philadelphia. 

Bastin's  Botany 

Laboratory  Exercises  in  Botany.  By  the  late  Edson  S.  Bastin, 
M.  A.     Octavo,  536  pages,  with  87  plates.     Cloth,  ^2.00  net. 

Barton  and  Wells*  Medical  Thesaurus 

A  Thesaurus  of  Medical  Words  and  Phrases.  By  Wilfred  M, 
Barton,  M.  D.,  Assistant  Professor  of  Materia  Medica  and  Therapeutics, 
and  Walter  A.  Wells,  M.D.,  Demonstrator  of  Laryngology,  Georgetown 
University,  Washington,  D.  C.  i2mo,  534  pages.  Flexible  leather, 
$2.50  net;  thumb  indexed,  $3.00  net. 
A  e  rk        tj^'Tk.*!*  Fifth   Revised  Edition 

American  Pocket  Dictionary  just  issued 

Dorland's  Pocket  Medical  Dictionary.  Edited  by  W.  A.  New- 
man DoRLAND,  M.  D.,  Assistant  Obstetrician  to  the  Hospital  of  the 
University  of  Pennsylvania.  Containing  the  pronunciation  and  defini- 
tion gf  the  principal  words  used  in  medicine  and  kindred  sciences,  with 
64  extensive  tables.  Handsomely  bound  in  flexible  leather,  with  gold 
edges,  $1.00  net;  with  patent  thumb  index,  $1.25  net. 

"  I  can  recommend  it  to  our  students  without  r«a«i-ve." — J.  H.  Holland,  M.  D., 
^the  Jefferson  Medical  College,  Philade^)liia. 


COLUMBIA  UNIVERSITY 

This  book  is  due  on  the  date  indicated' below,  or  at  the 
expiration  of  a  definite  period  after  the  date  of  borrowing, 
as  provided  by  the  rules  of  the  Library  or  by  special  ar- 
rangement with  the  Librarian  in  charge. 

DATE  BORROWED 

DATE  DUE 

DATE  BORROWED 

DATE  DUE 

■'■'    -     ■:    >^r 

1 

i 
1 

CZS(63S)M50 

